rs2837042

Positions:

• chr21-39475688-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BGR	NM_007341.3	c.312+473C>T		intron_variant		ENST00000333634.10
GET1-SH3BGR	NR_146618.2	n.1461+473C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BGR	ENST00000333634.10	c.312+473C>T		intron_variant		1	NM_007341.3	P1

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

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.138

Alfa AF: 0.167 Hom.: 2916

Bravo AF: 0.134

Asia WGS AF: 0.137 AC: 474 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	8.2
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: rs2837042; hg19: chr21-40847614;