rs2837042

Variant names:

• chr21-39475688-C-T
• rs2837042
• NM_007341.3:c.312+473C>T

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+473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,116 control chromosomes in the GnomAD database, including 1,986 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 0.15 (1986 hom., cov: 32)
• Consequence: SH3BGR NM_007341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.826
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007341.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BGR	NM_007341.3	MANE Select	c.312+473C>T		intron	N/A	NP_031367.2
	GET1-SH3BGR	NM_001317744.2		c.603+473C>T		intron	N/A	NP_001304673.1
	GET1-SH3BGR	NM_001350300.2		c.603+473C>T		intron	N/A	NP_001337229.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BGR	ENST00000333634.10	TSL:1 MANE Select	c.312+473C>T		intron	N/A	ENSP00000332513.5
	GET1-SH3BGR	ENST00000647779.1		c.603+473C>T		intron	N/A	ENSP00000497977.1
	SH3BGR	ENST00000452550.5	TSL:5	c.285+473C>T		intron	N/A	ENSP00000405675.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22766 AN: 151998 Hom.: 1988 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.150 AC: 22764 AN: 152116 Hom.: 1986 Cov.: 32 AF XY: 0.153 AC XY: 11356 AN XY: 74344

African (AFR) AF: 0.0833 AC: 3459 AN: 41516

American (AMR) AF: 0.100 AC: 1532 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3468

East Asian (EAS) AF: 0.119 AC: 617 AN: 5180

South Asian (SAS) AF: 0.210 AC: 1015 AN: 4824

European-Finnish (FIN) AF: 0.273 AC: 2882 AN: 10542

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12038 AN: 67978

Other (OTH) AF: 0.138 AC: 292 AN: 2114

Alfa AF: 0.165 Hom.: 3772

Bravo AF: 0.134

Asia WGS AF: 0.137 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.2
DANN	Benign	0.72
PhyloP100		0.83
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: rs2837042; hg19: chr21-40847614;