rs826423

chr3-15300094-G-Achr3-15300094-G-Cchr3-15300094-G-T

Variant summary

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

The NM_004844.5(SH3BP5):c.330+4009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,840 control chromosomes in the GnomAD database, including 23,920 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 0.55 (23920 hom., cov: 31)
• Consequence: SH3BP5 NM_004844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BP5	NM_004844.5	c.330+4009C>T		intron_variant		ENST00000383791.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP5	ENST00000383791.8	c.330+4009C>T		intron_variant		1	NM_004844.5	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83746 AN: 151722 Hom.: 23887 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.552 AC: 83830 AN: 151840 Hom.: 23920 Cov.: 31 AF XY: 0.551 AC XY: 40849 AN XY: 74188

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.538

Alfa AF: 0.502 Hom.: 12909

Bravo AF: 0.558

Asia WGS AF: 0.516 AC: 1798 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.51
Dann	Benign	0.21

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: rs826423; hg19: chr3-15341601;