Variant 11-68934444-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002180.3(IGHMBP2):c.1538-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,578,120 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 73 hom. )

Consequence

IGHMBP2
NM_002180.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.81

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:

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=-0.88).

BP6

Variant 11-68934444-C-T is Benign according to our data. Variant chr11-68934444-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68934444-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00278 (424/152324) while in subpopulation SAS AF= 0.0209 (101/4822). AF 95% confidence interval is 0.0176. There are 3 homozygotes in gnomad4. There are 222 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGHMBP2	NM_002180.3 linkuse as main transcript	c.1538-20C>T		intron_variant		ENST00000255078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGHMBP2	ENST00000255078.8 linkuse as main transcript	c.1538-20C>T		intron_variant		1	NM_002180.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00282

AC:

429

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0218

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00267

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00620

AC:

1353

AN:

218312

Hom.:

AF XY:

0.00778

AC XY:

916

AN XY:

117666

show subpopulations

Gnomad AFR exome

AF:

0.000897

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0143

Gnomad EAS exome

AF:

0.000124

Gnomad SAS exome

AF:

0.0293

Gnomad FIN exome

AF:

0.000946

Gnomad NFE exome

AF:

0.00324

Gnomad OTH exome

AF:

0.00583

GnomAD4 exome

AF:

0.00443

AC:

6310

AN:

1425796

Hom.:

Cov.:

AF XY:

0.00531

AC XY:

3763

AN XY:

708712

show subpopulations

Gnomad4 AFR exome

AF:

0.000981

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.000442

Gnomad4 SAS exome

AF:

0.0283

Gnomad4 FIN exome

AF:

0.000939

Gnomad4 NFE exome

AF:

0.00275

Gnomad4 OTH exome

AF:

0.00544

GnomAD4 genome

AF:

0.00278

AC:

424

AN:

152324

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00268

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00254

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 01, 2023	- -
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

Likely 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

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.27

DANN

Benign

0.73

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