rs2837043

Positions:

• chr21-39479630-T-G
• chr21-39479630-T-A
• chr21-39479630-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000333634.10(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 ENST00000333634.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SH3BGR	NM_007341.3	c.312+4415T>G		intron_variant		ENST00000333634.10	NP_031367.2
GET1-SH3BGR	NR_146618.2	n.1461+4415T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BGR	ENST00000333634.10	c.312+4415T>G		intron_variant		1	NM_007341.3	ENSP00000332513	P1

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.462

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

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

Other links and lift over

dbSNP: rs2837043; hg19: chr21-40851556;