rs117061430

Variant names:

• chr11-68906133-C-G
• rs117061430
• NM_002180.3:c.151C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-68906133-C-G
• chr11-68906133-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002180.3(IGHMBP2):​c.151C>G​(p.Gln51Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00594 in 1,614,180 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (41 hom.)
• Consequence: IGHMBP2 NM_002180.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 3.85
• Publications: 9 publications found

Genes affected

IGHMBP2 (HGNC:5542): (immunoglobulin mu DNA binding protein 2) This gene encodes a helicase superfamily member that binds a specific DNA sequence from the immunoglobulin mu chain switch region. Mutations in this gene lead to spinal muscle atrophy with respiratory distress type 1. [provided by RefSeq, Jul 2008]

IGHMBP2 Gene-Disease associations (from GenCC):

• autosomal recessive distal spinal muscular atrophy 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease axonal type 2S

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary peripheral neuropathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0074187815).
• BP6: Variant 11-68906133-C-G is Benign according to our data. Variant chr11-68906133-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00487 (741/152306) while in subpopulation NFE AF = 0.00691 (470/68022). AF 95% confidence interval is 0.00639. There are 6 homozygotes in GnomAd4. There are 389 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002180.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHMBP2	NM_002180.3	MANE Select	c.151C>G	p.Gln51Glu	missense	Exon 2 of 15	NP_002171.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHMBP2	ENST00000255078.8	TSL:1 MANE Select	c.151C>G	p.Gln51Glu	missense	Exon 2 of 15	ENSP00000255078.4
	IGHMBP2	ENST00000675615.1		c.151C>G	p.Gln51Glu	missense	Exon 2 of 14	ENSP00000502413.1
	IGHMBP2	ENST00000539224.2	TSL:3	n.112C>G		non_coding_transcript_exon	Exon 2 of 8	ENSP00000440465.2

Frequencies

GnomAD3 genomes AF: 0.00488 AC: 742 AN: 152188 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00691

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00606 AC: 1525 AN: 251490 AF XY: 0.00604

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0184

Gnomad NFE exome AF: 0.00839

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00606 AC: 8853 AN: 1461874 Hom.: 41 Cov.: 31 AF XY: 0.00592 AC XY: 4305 AN XY: 727242

African (AFR) AF: 0.00114 AC: 38 AN: 33480

American (AMR) AF: 0.00148 AC: 66 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00248 AC: 214 AN: 86258

European-Finnish (FIN) AF: 0.0183 AC: 975 AN: 53418

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.00655 AC: 7281 AN: 1111998

Other (OTH) AF: 0.00439 AC: 265 AN: 60396

GnomAD4 genome AF: 0.00487 AC: 741 AN: 152306 Hom.: 6 Cov.: 32 AF XY: 0.00522 AC XY: 389 AN XY: 74478

African (AFR) AF: 0.00123 AC: 51 AN: 41568

American (AMR) AF: 0.00163 AC: 25 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4828

European-Finnish (FIN) AF: 0.0161 AC: 171 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00691 AC: 470 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00562 Hom.: 3

Bravo AF: 0.00378

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00687 AC: 59

ExAC AF: 0.00628 AC: 762

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00583

EpiControl AF: 0.00557

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Dec 22, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 04, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Autosomal recessive distal spinal muscular atrophy 1 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Mar 11, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Aug 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IGHMBP2: BS2

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Charcot-Marie-Tooth disease Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

IGHMBP2-related disorder Benign:1

Apr 27, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Autosomal recessive distal spinal muscular atrophy 1;C4015349:Charcot-Marie-Tooth disease axonal type 2S Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Benign	0.83
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.0074	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.20
Sift	Benign	0.97	T
Sift4G	Benign	0.92	T
Polyphen		0.0040	B
Vest4		0.45
MVP		0.83
MPC		0.21
ClinPred		0.015	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.51
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs117061430; hg19: chr11-68673601; COSMIC: COSV54820857; COSMIC: COSV54820857;