chr15-45181911-G-C

Variant names:

• chr15-45181911-G-C
• rs1648308
• NM_001394037.1:c.499-3605C>G

Variant summary

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

The NM_001394037.1(SHF):​c.499-3605C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,194 control chromosomes in the GnomAD database, including 14,165 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 0.39 (14165 hom., cov: 33)
• Consequence: SHF NM_001394037.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816
• Publications: 3 publications found

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]

LOC124903481 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHF	NM_001394037.1	c.499-3605C>G		intron_variant	Intron 1 of 6	ENST00000690270.1	NP_001380966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHF	ENST00000690270.1	c.499-3605C>G		intron_variant	Intron 1 of 6		NM_001394037.1	ENSP00000508579.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58649 AN: 152076 Hom.: 14165 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.0584

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.385 AC: 58640 AN: 152194 Hom.: 14165 Cov.: 33 AF XY: 0.380 AC XY: 28302 AN XY: 74402

African (AFR) AF: 0.128 AC: 5316 AN: 41544

American (AMR) AF: 0.351 AC: 5366 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3472

East Asian (EAS) AF: 0.0582 AC: 302 AN: 5192

South Asian (SAS) AF: 0.327 AC: 1580 AN: 4828

European-Finnish (FIN) AF: 0.510 AC: 5390 AN: 10576

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37540 AN: 67968

Other (OTH) AF: 0.396 AC: 836 AN: 2112

Alfa AF: 0.332 Hom.: 1070

Bravo AF: 0.363

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		0.82
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: rs1648308; hg19: chr15-45474109;