chr17-48313716-C-T

Variant names:

• chr17-48313716-C-T
• rs12452212
• NM_003726.4:c.280+32189G>A

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+32189G>A 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 151,998 control chromosomes in the GnomAD database, including 9,161 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 (9161 hom., cov: 32)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 8 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=-0.54).
• 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+32189G>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+32189G>A		intron_variant	Intron 4 of 12	1	NM_003726.4	ENSP00000338171.6

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50694 AN: 151880 Hom.: 9152 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.334 AC: 50729 AN: 151998 Hom.: 9161 Cov.: 32 AF XY: 0.331 AC XY: 24582 AN XY: 74316

African (AFR) AF: 0.469 AC: 19437 AN: 41436

American (AMR) AF: 0.391 AC: 5968 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.177 AC: 916 AN: 5172

South Asian (SAS) AF: 0.186 AC: 897 AN: 4824

European-Finnish (FIN) AF: 0.268 AC: 2826 AN: 10548

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18630 AN: 67970

Other (OTH) AF: 0.314 AC: 663 AN: 2110

Alfa AF: 0.294 Hom.: 3501

Bravo AF: 0.354

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		0.098
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: rs12452212; hg19: chr17-46391078;