rs1287467

Positions:

• chr3-15269818-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004844.5(SH3BP5):​c.390T>C​(p.Arg130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 1,605,600 control chromosomes in the GnomAD database, including 356,041 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 0.63 (31205 hom., cov: 33)
  • Exomes 𝑓: 0.66 (324836 hom.)
• Consequence: SH3BP5 NM_004844.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

Genes affected

SH3BP5 (HGNC:10827): (SH3 domain binding protein 5) Enables guanyl-nucleotide exchange factor activity and protein kinase inhibitor activity. Acts upstream of or within intracellular signal transduction. Located in cytoplasmic vesicle membrane and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP7: Synonymous conserved (PhyloP=-3.26 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3BP5	NM_004844.5	c.390T>C	p.Arg130=	synonymous_variant	4/9	ENST00000383791.8	NP_004835.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BP5	ENST00000383791.8	c.390T>C	p.Arg130=	synonymous_variant	4/9	1	NM_004844.5	ENSP00000373301	P1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95948 AN: 152050 Hom.: 31190 Cov.: 33

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.659

GnomAD3 exomes AF: 0.584 AC: 144285 AN: 247130 Hom.: 45703 AF XY: 0.596 AC XY: 79682 AN XY: 133664

Gnomad AFR exome AF: 0.617

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.725

Gnomad EAS exome AF: 0.167

Gnomad SAS exome AF: 0.549

Gnomad FIN exome AF: 0.641

Gnomad NFE exome AF: 0.689

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.659 AC: 957730 AN: 1453432 Hom.: 324836 Cov.: 45 AF XY: 0.657 AC XY: 474748 AN XY: 722088

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.409

Gnomad4 ASJ exome AF: 0.723

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.558

Gnomad4 FIN exome AF: 0.636

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.631 AC: 95995 AN: 152168 Hom.: 31205 Cov.: 33 AF XY: 0.622 AC XY: 46249 AN XY: 74406

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.651

Alfa AF: 0.680 Hom.: 39105

Bravo AF: 0.621

Asia WGS AF: 0.353 AC: 1230 AN: 3478

EpiCase AF: 0.703

EpiControl AF: 0.715

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.062
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1287467; hg19: chr3-15311325; COSMIC: COSV53742917; COSMIC: COSV53742917;