rs6135

Variant names:

• chr1-169597088-G-A
• rs6135
• NM_003005.4:c.1794C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003005.4(SELP):​c.1794C>T​(p.Cys598Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,607,158 control chromosomes in the GnomAD database, including 22,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (7157 hom., cov: 32)
  • Exomes 𝑓: 0.12 (14927 hom.)
• Consequence: SELP NM_003005.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0220

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-169597088-G-A is Benign according to our data. Variant chr1-169597088-G-A is described in ClinVar as [Benign]. Clinvar id is 3056728.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.022 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.1794C>T	p.Cys598Cys	synonymous_variant	Exon 11 of 17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.1794C>T	p.Cys598Cys	synonymous_variant	Exon 11 of 17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34744 AN: 151986 Hom.: 7143 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.200

GnomAD3 exomes AF: 0.113 AC: 27913 AN: 247452 Hom.: 3747 AF XY: 0.102 AC XY: 13685 AN XY: 133782

Gnomad AFR exome AF: 0.568

Gnomad AMR exome AF: 0.0914

Gnomad ASJ exome AF: 0.0861

Gnomad EAS exome AF: 0.000653

Gnomad SAS exome AF: 0.0231

Gnomad FIN exome AF: 0.0771

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.117 AC: 170868 AN: 1455054 Hom.: 14927 Cov.: 33 AF XY: 0.113 AC XY: 81713 AN XY: 723814

Gnomad4 AFR exome AF: 0.571

Gnomad4 AMR exome AF: 0.0986

Gnomad4 ASJ exome AF: 0.0904

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.0235

Gnomad4 FIN exome AF: 0.0797

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.229 AC: 34804 AN: 152104 Hom.: 7157 Cov.: 32 AF XY: 0.220 AC XY: 16394 AN XY: 74360

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.0767

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.201

Alfa AF: 0.147 Hom.: 3313

Bravo AF: 0.252

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SELP-related disorder Benign:1

Nov 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.0
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs6135; hg19: chr1-169566326;