17-48292094-C-T

Variant names:

• chr17-48292094-C-T
• rs7218563
• NM_003726.4:c.280+53811G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.280+53811G>A		intron_variant	Intron 4 of 12	ENST00000336915.11	NP_003717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11	c.280+53811G>A		intron_variant	Intron 4 of 12	1	NM_003726.4	ENSP00000338171.6

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

African (AFR) AF: 0.767 AC: 30208 AN: 39366

American (AMR) AF: 0.640 AC: 9184 AN: 14350

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2104 AN: 3396

East Asian (EAS) AF: 0.454 AC: 2173 AN: 4786

South Asian (SAS) AF: 0.410 AC: 1795 AN: 4380

European-Finnish (FIN) AF: 0.602 AC: 5032 AN: 8356

Middle Eastern (MID) AF: 0.599 AC: 163 AN: 272

European-Non Finnish (NFE) AF: 0.574 AC: 37361 AN: 65034

Other (OTH) AF: 0.600 AC: 1176 AN: 1960

Alfa AF: 0.471 Hom.: 1366

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
PhyloP100		2.4
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: rs7218563; hg19: chr17-46369456;