rs2162246

Variant names:

• chr15-45169203-A-G
• rs2162246
• NM_001394037.1:c.1281-1070T>C

Variant summary

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

The NM_001394037.1(SHF):​c.1281-1070T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,086 control chromosomes in the GnomAD database, including 14,533 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 (14533 hom., cov: 32)
• Consequence: SHF NM_001394037.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 1 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHF	NM_001394037.1	c.1281-1070T>C		intron_variant	Intron 6 of 6	ENST00000690270.1	NP_001380966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHF	ENST00000690270.1	c.1281-1070T>C		intron_variant	Intron 6 of 6		NM_001394037.1	ENSP00000508579.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59562 AN: 151968 Hom.: 14533 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.392 AC: 59549 AN: 152086 Hom.: 14533 Cov.: 32 AF XY: 0.387 AC XY: 28754 AN XY: 74340

African (AFR) AF: 0.134 AC: 5554 AN: 41488

American (AMR) AF: 0.350 AC: 5346 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1515 AN: 3470

East Asian (EAS) AF: 0.0590 AC: 306 AN: 5184

South Asian (SAS) AF: 0.357 AC: 1718 AN: 4816

European-Finnish (FIN) AF: 0.521 AC: 5497 AN: 10554

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37952 AN: 67966

Other (OTH) AF: 0.404 AC: 853 AN: 2112

Alfa AF: 0.434 Hom.: 2510

Bravo AF: 0.367

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.82
PhyloP100		0.030
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: rs2162246; hg19: chr15-45461401;