3-15305786-C-T

Variant names:

• chr3-15305786-C-T
• rs9837421
• NM_004844.5:c.202-1555G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004844.5(SH3BP5):​c.202-1555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,842 control chromosomes in the GnomAD database, including 24,617 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 0.56 (24617 hom., cov: 31)
• Consequence: SH3BP5 NM_004844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004844.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	NM_004844.5	MANE Select	c.202-1555G>A		intron	N/A	NP_004835.2
	SH3BP5	NM_001018009.4		c.-338-1487G>A		intron	N/A	NP_001018009.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	ENST00000383791.8	TSL:1 MANE Select	c.202-1555G>A		intron	N/A	ENSP00000373301.3
	SH3BP5	ENST00000408919.7	TSL:1	c.-338-1487G>A		intron	N/A	ENSP00000386231.3
	SH3BP5	ENST00000426925.5	TSL:2	c.-631-1555G>A		intron	N/A	ENSP00000388553.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85328 AN: 151720 Hom.: 24574 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.563 AC: 85429 AN: 151842 Hom.: 24617 Cov.: 31 AF XY: 0.561 AC XY: 41597 AN XY: 74194

African (AFR) AF: 0.652 AC: 26969 AN: 41384

American (AMR) AF: 0.520 AC: 7933 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2082 AN: 3472

East Asian (EAS) AF: 0.825 AC: 4258 AN: 5162

South Asian (SAS) AF: 0.621 AC: 2985 AN: 4810

European-Finnish (FIN) AF: 0.460 AC: 4836 AN: 10522

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.510 AC: 34627 AN: 67920

Other (OTH) AF: 0.554 AC: 1168 AN: 2110

Alfa AF: 0.534 Hom.: 43186

Bravo AF: 0.569

Asia WGS AF: 0.721 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.77
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9837421; hg19: chr3-15347293;