chr21-39479630-T-G

Variant names:

• chr21-39479630-T-G
• rs2837043
• NM_007341.3:c.312+4415T>G

Variant summary

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

The NM_007341.3(SH3BGR):​c.312+4415T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,994 control chromosomes in the GnomAD database, including 16,879 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 0.43 (16879 hom., cov: 31)
• Consequence: SH3BGR NM_007341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 4 publications found

Genes affected

SH3BGR (HGNC:10822): (SH3 domain binding glutamate rich protein) Predicted to enable SH3 domain binding activity. Predicted to be involved in protein-containing complex assembly. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

GET1-SH3BGR (HGNC:54635): (GET1-SH3BGR readthrough) This locus represents naturally occurring readthrough transcription between the neighboring WRB (tryptophan rich basic protein) and SH3BGR (SH3 domain binding glutamate-rich protein) genes on chromosome 21. Readthrough transcripts may encode fusion proteins that shares sequence identity with each individual gene product. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BGR	NM_007341.3	c.312+4415T>G		intron_variant	Intron 3 of 6	ENST00000333634.10	NP_031367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BGR	ENST00000333634.10	c.312+4415T>G		intron_variant	Intron 3 of 6	1	NM_007341.3	ENSP00000332513.5
GET1-SH3BGR	ENST00000647779.1	c.603+4415T>G		intron_variant	Intron 5 of 8			ENSP00000497977.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65067 AN: 151876 Hom.: 16868 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.428 AC: 65085 AN: 151994 Hom.: 16879 Cov.: 31 AF XY: 0.435 AC XY: 32308 AN XY: 74292

African (AFR) AF: 0.121 AC: 5032 AN: 41498

American (AMR) AF: 0.586 AC: 8958 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3466

East Asian (EAS) AF: 0.679 AC: 3500 AN: 5156

South Asian (SAS) AF: 0.513 AC: 2461 AN: 4794

European-Finnish (FIN) AF: 0.517 AC: 5456 AN: 10548

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.535 AC: 36347 AN: 67938

Other (OTH) AF: 0.462 AC: 974 AN: 2108

Alfa AF: 0.326 Hom.: 955

Bravo AF: 0.422

Asia WGS AF: 0.597 AC: 2078 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.86
PhyloP100		-0.025
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: rs2837043; hg19: chr21-40851556;