rs7207826

Positions:

• chr17-48423311-T-C

Variant summary

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

The NM_003726.4(SKAP1):​c.46+6764A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,942 control chromosomes in the GnomAD database, including 8,975 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 (8975 hom., cov: 31)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.46+6764A>G		intron_variant		ENST00000336915.11	NP_003717.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKAP1	ENST00000336915.11	c.46+6764A>G		intron_variant		1	NM_003726.4	ENSP00000338171	P1
SKAP1	ENST00000584924.5	c.46+6764A>G		intron_variant		2		ENSP00000464311	P1
SKAP1	ENST00000584709.5	c.46+6764A>G		intron_variant, NMD_transcript_variant		2		ENSP00000463284

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50052 AN: 151824 Hom.: 8965 Cov.: 31

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.330 AC: 50090 AN: 151942 Hom.: 8975 Cov.: 31 AF XY: 0.327 AC XY: 24302 AN XY: 74286

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.311

Alfa AF: 0.310 Hom.: 1337

Bravo AF: 0.349

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.65

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: rs7207826; hg19: chr17-46500673;