rs826423

Variant names:

• chr3-15300094-G-A
• rs826423
• NM_004844.5:c.330+4009C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-15300094-G-A
• chr3-15300094-G-C
• chr3-15300094-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	NM_004844.5	MANE Select	c.330+4009C>T		intron	N/A	NP_004835.2	O60239-1
	SH3BP5	NM_001018009.4		c.-142+4009C>T		intron	N/A	NP_001018009.2	O60239-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	ENST00000383791.8	TSL:1 MANE Select	c.330+4009C>T		intron	N/A	ENSP00000373301.3	O60239-1
	SH3BP5	ENST00000408919.7	TSL:1	c.-142+4009C>T		intron	N/A	ENSP00000386231.3	O60239-2
	SH3BP5	ENST00000947043.1		c.330+4009C>T		intron	N/A	ENSP00000617102.1

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

African (AFR) AF: 0.709 AC: 29351 AN: 41396

American (AMR) AF: 0.457 AC: 6980 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3468

East Asian (EAS) AF: 0.529 AC: 2725 AN: 5154

South Asian (SAS) AF: 0.512 AC: 2467 AN: 4814

European-Finnish (FIN) AF: 0.504 AC: 5304 AN: 10516

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33556 AN: 67924

Other (OTH) AF: 0.538 AC: 1135 AN: 2108

Alfa AF: 0.524 Hom.: 18839

Bravo AF: 0.558

Asia WGS AF: 0.516 AC: 1798 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.21
PhyloP100		-0.72
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: rs826423; hg19: chr3-15341601;