17-48261388-G-C

Position:

• chr17-48261388-G-C

Variant summary

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

The NM_003726.4(SKAP1):​c.281-71888C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,082 control chromosomes in the GnomAD database, including 47,810 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 0.79 (47810 hom., cov: 31)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

Genes affected

SKAP1 (HGNC:15605): (src kinase associated phosphoprotein 1) This gene encodes a T cell adaptor protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a PH domain and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adaptor protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKAP1	NM_003726.4	c.281-71888C>G		intron_variant		ENST00000336915.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKAP1	ENST00000336915.11	c.281-71888C>G		intron_variant		1	NM_003726.4	P1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120307 AN: 151964 Hom.: 47759 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.866

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.792 AC: 120417 AN: 152082 Hom.: 47810 Cov.: 31 AF XY: 0.797 AC XY: 59226 AN XY: 74346

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.950

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.777

Alfa AF: 0.681 Hom.: 1892

Bravo AF: 0.793

Asia WGS AF: 0.914 AC: 3179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.40

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: rs2938471; hg19: chr17-46338750;