1-169630016-T-C

Variant names:

• chr1-169630016-T-C
• rs732314
• NM_003005.4:c.3+56A>G

Variant summary

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

The NM_003005.4(SELP):​c.3+56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,610,560 control chromosomes in the GnomAD database, including 206,585 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 0.52 (21453 hom., cov: 32)
  • Exomes 𝑓: 0.50 (185132 hom.)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.3+56A>G		intron_variant	Intron 1 of 16	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.3+56A>G		intron_variant	Intron 1 of 16	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79478 AN: 151908 Hom.: 21420 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.500 AC: 729521 AN: 1458534 Hom.: 185132 AF XY: 0.497 AC XY: 360603 AN XY: 725678

African (AFR) AF: 0.641 AC: 21417 AN: 33400

American (AMR) AF: 0.388 AC: 17357 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 14518 AN: 26118

East Asian (EAS) AF: 0.321 AC: 12759 AN: 39692

South Asian (SAS) AF: 0.394 AC: 33932 AN: 86184

European-Finnish (FIN) AF: 0.465 AC: 24808 AN: 53398

Middle Eastern (MID) AF: 0.595 AC: 3431 AN: 5764

European-Non Finnish (NFE) AF: 0.515 AC: 570702 AN: 1109000

Other (OTH) AF: 0.508 AC: 30597 AN: 60274

GnomAD4 genome AF: 0.523 AC: 79559 AN: 152026 Hom.: 21453 Cov.: 32 AF XY: 0.517 AC XY: 38416 AN XY: 74300

African (AFR) AF: 0.634 AC: 26289 AN: 41460

American (AMR) AF: 0.441 AC: 6724 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3466

East Asian (EAS) AF: 0.344 AC: 1782 AN: 5174

South Asian (SAS) AF: 0.374 AC: 1803 AN: 4820

European-Finnish (FIN) AF: 0.459 AC: 4843 AN: 10560

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.508 AC: 34518 AN: 67972

Other (OTH) AF: 0.525 AC: 1106 AN: 2108

Alfa AF: 0.512 Hom.: 33070

Bravo AF: 0.528

Asia WGS AF: 0.356 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.41
PhyloP100		0.0060
PromoterAI		-0.0053	Neutral
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: rs732314; hg19: chr1-169599254; COSMIC: COSV107224837;