11-68918811-C-G

Variant names:

• chr11-68918811-C-G
• rs654797
• NM_002180.3:c.1060+928C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002180.3(IGHMBP2):​c.1060+928C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,132 control chromosomes in the GnomAD database, including 44,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44546 hom., cov: 32)
• Consequence: IGHMBP2 NM_002180.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGHMBP2	NM_002180.3	c.1060+928C>G		intron_variant	Intron 7 of 14	ENST00000255078.8	NP_002171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078.8	c.1060+928C>G		intron_variant	Intron 7 of 14	1	NM_002180.3	ENSP00000255078.4

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114983 AN: 152014 Hom.: 44517 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.786

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.756 AC: 115063 AN: 152132 Hom.: 44546 Cov.: 32 AF XY: 0.755 AC XY: 56156 AN XY: 74358

African (AFR) AF: 0.619 AC: 25670 AN: 41468

American (AMR) AF: 0.826 AC: 12629 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2762 AN: 3472

East Asian (EAS) AF: 0.484 AC: 2494 AN: 5156

South Asian (SAS) AF: 0.728 AC: 3510 AN: 4824

European-Finnish (FIN) AF: 0.757 AC: 8021 AN: 10594

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.842 AC: 57260 AN: 68008

Other (OTH) AF: 0.784 AC: 1654 AN: 2110

Alfa AF: 0.750 Hom.: 2682

Bravo AF: 0.755

Asia WGS AF: 0.620 AC: 2157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.44
DANN	Benign	0.58
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs654797; hg19: chr11-68686279;