Variant 11-68933499-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002180.3(IGHMBP2):c.1418+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,603,258 control chromosomes in the GnomAD database, including 1,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 736 hom., cov: 33)

Exomes 𝑓: 0.015 ( 867 hom. )

Consequence

IGHMBP2
NM_002180.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.04

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 links:

IGHMBP2 (HGNC:):

IGHMBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-68933499-A-G is Benign according to our data. Variant chr11-68933499-A-G is described in ClinVar as [Benign]. Clinvar id is 258556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68933499-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGHMBP2	NM_002180.3 linkuse as main transcript	c.1418+18A>G		intron_variant		ENST00000255078.8	NP_002171.2	P38935

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGHMBP2	ENST00000255078.8 linkuse as main transcript	c.1418+18A>G		intron_variant		1	NM_002180.3	ENSP00000255078.4		P38935

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9037

AN:

151986

Hom.:

725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.0116

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00841

Gnomad OTH

AF:

0.0566

GnomAD3 exomes

AF:

0.0227

AC:

5212

AN:

229142

Hom.:

268

AF XY:

0.0210

AC XY:

2620

AN XY:

124508

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00517

Gnomad SAS exome

AF:

0.0282

Gnomad FIN exome

AF:

0.00309

Gnomad NFE exome

AF:

0.00857

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0146

AC:

21163

AN:

1451154

Hom.:

867

Cov.:

AF XY:

0.0145

AC XY:

10431

AN XY:

721046

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.0181

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.0284

Gnomad4 SAS exome

AF:

0.0267

Gnomad4 FIN exome

AF:

0.00280

Gnomad4 NFE exome

AF:

0.00738

Gnomad4 OTH exome

AF:

0.0243

GnomAD4 genome

AF:

0.0597

AC:

9085

AN:

152104

Hom.:

736

Cov.:

AF XY:

0.0587

AC XY:

4362

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.0317

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.0116

Gnomad4 SAS

AF:

0.0278

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.00844

Gnomad4 OTH

AF:

0.0598

Alfa

AF:

0.0314

Hom.:

Bravo

AF:

0.0661

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.18

DANN

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over