rs6504145

Positions:

• chr17-48263229-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003726.4(SKAP1):​c.281-73729G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,006 control chromosomes in the GnomAD database, including 3,343 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 0.21 (3343 hom., cov: 32)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.281-73729G>A		intron_variant		ENST00000336915.11	NP_003717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11	c.281-73729G>A		intron_variant		1	NM_003726.4	ENSP00000338171.6

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31848 AN: 151886 Hom.: 3343 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.210 AC: 31864 AN: 152006 Hom.: 3343 Cov.: 32 AF XY: 0.210 AC XY: 15607 AN XY: 74286

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.202

Alfa AF: 0.212 Hom.: 881

Bravo AF: 0.209

Asia WGS AF: 0.187 AC: 652 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.61

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: rs6504145; hg19: chr17-46340591;