rs3959644

Positions:

• chr15-45195934-G-T

Variant summary

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

The NM_138356.3(SHF):​c.303+2838C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,992 control chromosomes in the GnomAD database, including 9,212 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 0.33 (9212 hom., cov: 33)
• Consequence: SHF NM_138356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

Genes affected

SHF (HGNC:25116): (Src homology 2 domain containing F) Predicted to enable phosphotyrosine residue binding activity. Predicted to be involved in apoptotic process. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259519 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHF	NM_138356.3	c.303+2838C>A		intron_variant			NP_612365.3
SHF	NM_001394041.1	c.303+2838C>A		intron_variant			NP_001380970.1
SHF	NM_001394043.1	c.303+2838C>A		intron_variant			NP_001380972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHF	ENST00000290894.12	c.303+2838C>A		intron_variant		2		ENSP00000290894.8
SHF	ENST00000561278.1	c.-109+4793C>A		intron_variant		4		ENSP00000453986.1
ENSG00000259519	ENST00000560034.1	n.192-3924G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49708 AN: 151874 Hom.: 9196 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.327 AC: 49740 AN: 151992 Hom.: 9212 Cov.: 33 AF XY: 0.333 AC XY: 24754 AN XY: 74288

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.358

Alfa AF: 0.351 Hom.: 15018

Bravo AF: 0.330

Asia WGS AF: 0.458 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.8
DANN	Benign	0.72

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: rs3959644; hg19: chr15-45488132;