1-169596108-C-G

Variant names:

• chr1-169596108-C-G
• rs6133
• NM_003005.4:c.1918G>C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP6

The NM_003005.4(SELP):​c.1918G>C​(p.Val640Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.576

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

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08592385).
• BP6: Variant 1-169596108-C-G is Benign according to our data. Variant chr1-169596108-C-G is described in ClinVar as [Benign]. Clinvar id is 13528.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.1918G>C	p.Val640Leu	missense_variant	Exon 12 of 17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.1918G>C	p.Val640Leu	missense_variant	Exon 12 of 17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SELECTIN P POLYMORPHISM Benign:1

Sep 01, 2003

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.013	T;.;T;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T;T;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.086	T;T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.89	N;N;N;.;N
REVEL	Benign	0.0050
Sift	Benign	0.15	T;T;T;.;T
Sift4G	Benign	0.25	T;T;T;T;T
Vest4		0.23, 0.078, 0.22, 0.074
MutPred		0.37		.;Gain of glycosylation at P638 (P = 0.0801);.;.;.;
MVP		0.081
MPC		0.061
ClinPred		0.16	T
GERP RS		3.2
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6133; hg19: chr1-169565346;