rs2292468

chr15-45174894-A-G

Variant summary

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

The NM_001394037.1(SHF):c.847+325T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,958 control chromosomes in the GnomAD database, including 17,897 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 0.48 (17897 hom., cov: 31)
• Consequence: SHF NM_001394037.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHF	NM_001394037.1	c.847+325T>C		intron_variant		ENST00000690270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHF	ENST00000690270.1	c.847+325T>C		intron_variant			NM_001394037.1	P1
	ENST00000560034.1	n.191+4360A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72817 AN: 151840 Hom.: 17873 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.480 AC: 72884 AN: 151958 Hom.: 17897 Cov.: 31 AF XY: 0.488 AC XY: 36207 AN XY: 74270

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.502

Alfa AF: 0.482 Hom.: 3664

Bravo AF: 0.487

Asia WGS AF: 0.630 AC: 2190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	8.4
Dann	Benign	0.87

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: rs2292468; hg19: chr15-45467092;