chr21-39475085-T-C

Position:

• chr21-39475085-T-C

Variant summary

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

The NM_007341.3(SH3BGR):​c.232-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,115,488 control chromosomes in the GnomAD database, including 57,770 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 0.34 (9533 hom., cov: 32)
  • Exomes 𝑓: 0.31 (48237 hom.)
• Consequence: SH3BGR NM_007341.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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]

GET1-SH3BGR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3BGR	NM_007341.3	c.232-50T>C		intron_variant		ENST00000333634.10	NP_031367.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BGR	ENST00000333634.10	c.232-50T>C		intron_variant		1	NM_007341.3	ENSP00000332513.5
GET1-SH3BGR	ENST00000647779.1	c.523-50T>C		intron_variant				ENSP00000497977.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52070 AN: 151948 Hom.: 9525 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.321

GnomAD3 exomes AF: 0.294 AC: 61750 AN: 210064 Hom.: 9955 AF XY: 0.299 AC XY: 34216 AN XY: 114468

Gnomad AFR exome AF: 0.445

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.327

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.319

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.309 AC: 297880 AN: 963422 Hom.: 48237 Cov.: 12 AF XY: 0.311 AC XY: 154152 AN XY: 496184

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.173

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.385

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.343 AC: 52103 AN: 152066 Hom.: 9533 Cov.: 32 AF XY: 0.342 AC XY: 25407 AN XY: 74324

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.322

Alfa AF: 0.318 Hom.: 8493

Bravo AF: 0.332

Asia WGS AF: 0.231 AC: 799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
DANN	Benign	0.74

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: rs874221; hg19: chr21-40847011;