17-48323291-A-G

Variant names:

• chr17-48323291-A-G
• rs4451990
• NM_003726.4:c.280+22614T>C

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+22614T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 151,584 control chromosomes in the GnomAD database, including 9,349 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 0.33 (9349 hom., cov: 31)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.280+22614T>C		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+22614T>C		intron_variant	Intron 4 of 12	1	NM_003726.4	ENSP00000338171.6

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50604 AN: 151466 Hom.: 9340 Cov.: 31

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.334 AC: 50640 AN: 151584 Hom.: 9349 Cov.: 31 AF XY: 0.331 AC XY: 24535 AN XY: 74098

African (AFR) AF: 0.469 AC: 19388 AN: 41332

American (AMR) AF: 0.393 AC: 5979 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.177 AC: 916 AN: 5168

South Asian (SAS) AF: 0.186 AC: 889 AN: 4784

European-Finnish (FIN) AF: 0.265 AC: 2767 AN: 10454

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18634 AN: 67842

Other (OTH) AF: 0.315 AC: 662 AN: 2104

Alfa AF: 0.299 Hom.: 20966

Bravo AF: 0.355

Asia WGS AF: 0.222 AC: 775 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.34
PhyloP100		0.13
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: rs4451990; hg19: chr17-46400653;