chr21-39453629-T-C

Variant names:

• chr21-39453629-T-C
• rs2837039
• NM_007341.3:c.45+1488T>C

Variant summary

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

The NM_007341.3(SH3BGR):​c.45+1488T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,196 control chromosomes in the GnomAD database, including 2,571 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 0.18 (2571 hom., cov: 32)
• Consequence: SH3BGR NM_007341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BGR	NM_007341.3	c.45+1488T>C		intron_variant	Intron 1 of 6	ENST00000333634.10	NP_031367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BGR	ENST00000333634.10	c.45+1488T>C		intron_variant	Intron 1 of 6	1	NM_007341.3	ENSP00000332513.5
GET1-SH3BGR	ENST00000647779.1	c.337-8746T>C		intron_variant	Intron 3 of 8			ENSP00000497977.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27326 AN: 152078 Hom.: 2568 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.180 AC: 27334 AN: 152196 Hom.: 2571 Cov.: 32 AF XY: 0.173 AC XY: 12886 AN XY: 74436

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.179

Alfa AF: 0.195 Hom.: 1383

Bravo AF: 0.180

Asia WGS AF: 0.112 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.72

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: rs2837039; hg19: chr21-40825555;