chr17-48271022-T-C

Variant names:

• chr17-48271022-T-C
• rs2924254
• NM_003726.4:c.280+74883A>G

Variant summary

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

The NM_003726.4(SKAP1):​c.280+74883A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,592 control chromosomes in the GnomAD database, including 16,251 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 0.46 (16251 hom., cov: 29)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.280+74883A>G		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+74883A>G		intron_variant	Intron 4 of 12	1	NM_003726.4	ENSP00000338171.6

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69596 AN: 151472 Hom.: 16242 Cov.: 29

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.459 AC: 69641 AN: 151592 Hom.: 16251 Cov.: 29 AF XY: 0.464 AC XY: 34389 AN XY: 74082

African (AFR) AF: 0.403 AC: 16624 AN: 41258

American (AMR) AF: 0.498 AC: 7584 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3466

East Asian (EAS) AF: 0.571 AC: 2943 AN: 5150

South Asian (SAS) AF: 0.620 AC: 2979 AN: 4804

European-Finnish (FIN) AF: 0.472 AC: 4944 AN: 10476

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31526 AN: 67898

Other (OTH) AF: 0.472 AC: 992 AN: 2102

Alfa AF: 0.465 Hom.: 61915

Bravo AF: 0.458

Asia WGS AF: 0.598 AC: 2078 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.68
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2924254; hg19: chr17-46348384;