rs2084881

Variant names:

• chr17-48279758-G-A
• rs2084881
• NM_003726.4:c.280+66147C>T

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+66147C>T 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 151,996 control chromosomes in the GnomAD database, including 8,982 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 (8982 hom., cov: 31)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 25 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003726.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP1	NM_003726.4	MANE Select	c.280+66147C>T		intron	N/A	NP_003717.3
	SKAP1	NM_001075099.2		c.280+66147C>T		intron	N/A	NP_001068567.1	Q86WV1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP1	ENST00000336915.11	TSL:1 MANE Select	c.280+66147C>T		intron	N/A	ENSP00000338171.6	Q86WV1-1
	SKAP1	ENST00000970118.1		c.280+66147C>T		intron	N/A	ENSP00000640177.1
	SKAP1	ENST00000584924.5	TSL:2	c.280+66147C>T		intron	N/A	ENSP00000464311.1	Q86WV1-1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50071 AN: 151878 Hom.: 8974 Cov.: 31

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.330 AC: 50105 AN: 151996 Hom.: 8982 Cov.: 31 AF XY: 0.327 AC XY: 24280 AN XY: 74284

African (AFR) AF: 0.468 AC: 19371 AN: 41434

American (AMR) AF: 0.389 AC: 5935 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1014 AN: 3468

East Asian (EAS) AF: 0.178 AC: 921 AN: 5178

South Asian (SAS) AF: 0.184 AC: 888 AN: 4822

European-Finnish (FIN) AF: 0.263 AC: 2776 AN: 10536

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

European-Non Finnish (NFE) AF: 0.267 AC: 18178 AN: 67966

Other (OTH) AF: 0.313 AC: 661 AN: 2110

Alfa AF: 0.280 Hom.: 22578

Bravo AF: 0.350

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.0
DANN	Benign	0.88
PhyloP100		0.029
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: rs2084881; hg19: chr17-46357120;