chr17-48296309-C-T

Variant names:

• chr17-48296309-C-T
• rs7221510
• NM_003726.4:c.280+49596G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003726.4(SKAP1):​c.280+49596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,016 control chromosomes in the GnomAD database, including 26,690 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 0.59 (26690 hom., cov: 32)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 7 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]

SKAP1-AS2 (HGNC:55570): (SKAP1 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SKAP1	NM_003726.4	c.280+49596G>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+49596G>A		intron_variant	Intron 4 of 12	1	NM_003726.4	ENSP00000338171.6

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89430 AN: 151900 Hom.: 26681 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.589 AC: 89473 AN: 152016 Hom.: 26690 Cov.: 32 AF XY: 0.585 AC XY: 43456 AN XY: 74324

African (AFR) AF: 0.675 AC: 27993 AN: 41470

American (AMR) AF: 0.615 AC: 9391 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2043 AN: 3464

East Asian (EAS) AF: 0.431 AC: 2233 AN: 5176

South Asian (SAS) AF: 0.390 AC: 1879 AN: 4812

European-Finnish (FIN) AF: 0.580 AC: 6133 AN: 10570

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.557 AC: 37843 AN: 67936

Other (OTH) AF: 0.564 AC: 1191 AN: 2112

Alfa AF: 0.566 Hom.: 12305

Bravo AF: 0.600

Asia WGS AF: 0.416 AC: 1448 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.82
PhyloP100		2.7
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: rs7221510; hg19: chr17-46373671;