NM_003005.4:c.961+197T>C

Variant names:

• chr1-169612020-A-G
• rs3917727
• NM_003005.4:c.961+197T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003005.4(SELP):​c.961+197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,042 control chromosomes in the GnomAD database, including 6,272 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 0.28 (6272 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 19 publications found

Genes affected

SELP (HGNC:10721): (selectin P) This gene encodes a 140 kDa protein that is stored in the alpha-granules of platelets and Weibel-Palade bodies of endothelial cells. This protein redistributes to the plasma membrane during platelet activation and degranulation and mediates the interaction of activated endothelial cells or platelets with leukocytes. The membrane protein is a calcium-dependent receptor that binds to sialylated forms of Lewis blood group carbohydrate antigens on neutrophils and monocytes. Alternative splice variants may occur but are not well documented. [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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.961+197T>C		intron_variant	Intron 6 of 16	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.961+197T>C		intron_variant	Intron 6 of 16	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42426 AN: 151924 Hom.: 6269 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.279 AC: 42429 AN: 152042 Hom.: 6272 Cov.: 32 AF XY: 0.271 AC XY: 20160 AN XY: 74346

African (AFR) AF: 0.230 AC: 9539 AN: 41432

American (AMR) AF: 0.234 AC: 3574 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1037 AN: 3470

East Asian (EAS) AF: 0.0150 AC: 78 AN: 5184

South Asian (SAS) AF: 0.246 AC: 1187 AN: 4816

European-Finnish (FIN) AF: 0.274 AC: 2894 AN: 10578

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23074 AN: 67964

Other (OTH) AF: 0.296 AC: 623 AN: 2108

Alfa AF: 0.308 Hom.: 6180

Bravo AF: 0.272

Asia WGS AF: 0.116 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.54
PhyloP100		-0.76
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: rs3917727; hg19: chr1-169581258;