rs118015540

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002180.3(IGHMBP2):c.256+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00773 in 1,613,624 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 59 hom. )

Consequence

IGHMBP2
NM_002180.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.797

Publications

3 publications found

Variant links:

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

IGHMBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-68906247-G-A is Benign according to our data. Variant chr11-68906247-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 137568.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 = 0.00567 (863/152306) while in subpopulation NFE AF = 0.00938 (638/68026). AF 95% confidence interval is 0.00878. There are 4 homozygotes in GnomAd4. There are 386 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGHMBP2	NM_002180.3	MANE Select	c.256+9G>A		intron	N/A	NP_002171.2	P38935

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGHMBP2	ENST00000255078.8	TSL:1 MANE Select	c.256+9G>A	intron	N/A	ENSP00000255078.4	P38935
IGHMBP2	ENST00000925063.1		c.256+9G>A	intron	N/A	ENSP00000595122.1
IGHMBP2	ENST00000675615.1		c.256+9G>A	intron	N/A	ENSP00000502413.1	A0A6Q8PGT6

Frequencies

GnomAD3 genomes

AF:

0.00567

AC:

863

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00500

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00938

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00508

AC:

1277

AN:

251290

AF XY:

0.00511

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00298

Gnomad ASJ exome

AF:

0.000893

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00476

Gnomad NFE exome

AF:

0.00836

Gnomad OTH exome

AF:

0.00701

GnomAD4 exome

AF:

0.00795

AC:

11612

AN:

1461318

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

5648

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

33462

American (AMR)

AF:

0.00333

AC:

149

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

26130

East Asian (EAS)

AF:

0.000202

AC:

AN:

39698

South Asian (SAS)

AF:

0.000846

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00511

AC:

273

AN:

53410

Middle Eastern (MID)

AF:

0.00265

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00960

AC:

10669

AN:

1111650

Other (OTH)

AF:

0.00573

AC:

346

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

539

1078

1617

2156

2695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

396

792

1188

1584

1980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00567

AC:

863

AN:

152306

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

386

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41578

American (AMR)

AF:

0.00543

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00500

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00938

AC:

638

AN:

68026

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

136

182

227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00844

Hom.:

Bravo

AF:

0.00574

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Autosomal recessive distal spinal muscular atrophy 1 (2)

not provided (2)

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

Charcot-Marie-Tooth disease (1)

IGHMBP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

(source)

DANN

Benign

0.94

PhyloP100

-0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over