NM_003005.4:c.1918G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 15/20 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
• Publications: 60 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: Likely_benign. The variant received -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 VariationId is 13528.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003005.4. 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
	SELP	NM_003005.4	MANE Select	c.1918G>C	p.Val640Leu	missense	Exon 12 of 17	NP_002996.2	P16109

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	ENST00000263686.11	TSL:1 MANE Select	c.1918G>C	p.Val640Leu	missense	Exon 12 of 17	ENSP00000263686.5	P16109
	SELP	ENST00000426706.6	TSL:1	c.1915G>C	p.Val639Leu	missense	Exon 11 of 15	ENSP00000391694.2	Q5R349
	SELP	ENST00000909597.1		c.1918G>C	p.Val640Leu	missense	Exon 12 of 17	ENSP00000579656.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RECLASSIFIED - SELP POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.58
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.0050
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Vest4		0.23
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
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs6133; hg19: chr1-169565346;