rs1287467

Variant names:

• chr3-15269818-A-G
• rs1287467
• NM_004844.5:c.390T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-15269818-A-G
• chr3-15269818-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004844.5(SH3BP5):​c.390T>C​(p.Arg130Arg) 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
• Publications: 16 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 -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.

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.390T>C	p.Arg130Arg	synonymous	Exon 4 of 9	NP_004835.2
	SH3BP5	NM_001018009.4		c.-82T>C		5_prime_UTR	Exon 4 of 9	NP_001018009.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	ENST00000383791.8	TSL:1 MANE Select	c.390T>C	p.Arg130Arg	synonymous	Exon 4 of 9	ENSP00000373301.3
	SH3BP5	ENST00000408919.7	TSL:1	c.-82T>C		5_prime_UTR	Exon 4 of 9	ENSP00000386231.3
	SH3BP5	ENST00000450625.1	TSL:3	n.*248T>C		non_coding_transcript_exon	Exon 4 of 5	ENSP00000389484.1

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

GnomAD2 exomes AF: 0.584 AC: 144285 AN: 247130 AF XY: 0.596

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 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

African (AFR) AF: 0.622 AC: 20689 AN: 33236

American (AMR) AF: 0.409 AC: 17964 AN: 43964

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 18693 AN: 25868

East Asian (EAS) AF: 0.152 AC: 5995 AN: 39482

South Asian (SAS) AF: 0.558 AC: 47819 AN: 85700

European-Finnish (FIN) AF: 0.636 AC: 33871 AN: 53224

Middle Eastern (MID) AF: 0.690 AC: 3922 AN: 5682

European-Non Finnish (NFE) AF: 0.696 AC: 769828 AN: 1106318

Other (OTH) AF: 0.650 AC: 38949 AN: 59958

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

African (AFR) AF: 0.623 AC: 25863 AN: 41512

American (AMR) AF: 0.537 AC: 8218 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2536 AN: 3470

East Asian (EAS) AF: 0.172 AC: 892 AN: 5174

South Asian (SAS) AF: 0.526 AC: 2534 AN: 4822

European-Finnish (FIN) AF: 0.635 AC: 6730 AN: 10604

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46983 AN: 67970

Other (OTH) AF: 0.651 AC: 1378 AN: 2116

Alfa AF: 0.666 Hom.: 59397

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.062
DANN	Benign	0.48
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=294/6	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: rs1287467; hg19: chr3-15311325; COSMIC: COSV53742917; COSMIC: COSV53742917;