17-48292094-C-T

Position:

• chr17-48292094-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003726.4(SKAP1):​c.280+53811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 142,776 control chromosomes in the GnomAD database, including 28,268 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 0.63 (28268 hom., cov: 22)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SKAP1	NM_003726.4	c.280+53811G>A		intron_variant		ENST00000336915.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SKAP1	ENST00000336915.11	c.280+53811G>A		intron_variant		1	NM_003726.4	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 89726 AN: 142686 Hom.: 28236 Cov.: 22

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.629 AC: 89791 AN: 142776 Hom.: 28268 Cov.: 22 AF XY: 0.627 AC XY: 43257 AN XY: 69016

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.600

Alfa AF: 0.445 Hom.: 1138

Bravo AF: 0.630

Asia WGS AF: 0.421 AC: 1458 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.65

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: rs7218563; hg19: chr17-46369456;