NM_003726.4:c.280+29217C>T

Variant names:

• chr17-48316688-G-A
• rs7218167
• NM_003726.4:c.280+29217C>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+29217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,064 control chromosomes in the GnomAD database, including 2,315 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 0.17 (2315 hom., cov: 31)
• Consequence: SKAP1 NM_003726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP1	NM_003726.4	MANE Select	c.280+29217C>T		intron	N/A	NP_003717.3
	SKAP1	NM_001075099.2		c.280+29217C>T		intron	N/A	NP_001068567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SKAP1	ENST00000336915.11	TSL:1 MANE Select	c.280+29217C>T		intron	N/A	ENSP00000338171.6
	SKAP1	ENST00000584924.5	TSL:2	c.280+29217C>T		intron	N/A	ENSP00000464311.1
	SKAP1	ENST00000581400.2	TSL:5	n.100+29217C>T		intron	N/A	ENSP00000462360.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26223 AN: 151944 Hom.: 2316 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.172 AC: 26230 AN: 152064 Hom.: 2315 Cov.: 31 AF XY: 0.169 AC XY: 12555 AN XY: 74306

African (AFR) AF: 0.165 AC: 6834 AN: 41486

American (AMR) AF: 0.160 AC: 2442 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3470

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5182

South Asian (SAS) AF: 0.105 AC: 504 AN: 4816

European-Finnish (FIN) AF: 0.196 AC: 2073 AN: 10562

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12870 AN: 67982

Other (OTH) AF: 0.173 AC: 366 AN: 2112

Alfa AF: 0.176 Hom.: 376

Bravo AF: 0.170

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		0.40
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: rs7218167; hg19: chr17-46394050;