rs6135

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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 VariationId 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.

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.1794C>T	p.Cys598Cys	synonymous	Exon 11 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.1794C>T	p.Cys598Cys	synonymous	Exon 11 of 17	ENSP00000263686.5	P16109
	SELP	ENST00000426706.6	TSL:1	c.1791C>T	p.Cys597Cys	synonymous	Exon 10 of 15	ENSP00000391694.2	Q5R349
	SELP	ENST00000909597.1		c.1794C>T	p.Cys598Cys	synonymous	Exon 11 of 17	ENSP00000579656.1

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

GnomAD2 exomes AF: 0.113 AC: 27913 AN: 247452 AF XY: 0.102

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 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

African (AFR) AF: 0.571 AC: 18670 AN: 32702

American (AMR) AF: 0.0986 AC: 4353 AN: 44128

Ashkenazi Jewish (ASJ) AF: 0.0904 AC: 2337 AN: 25864

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39688

South Asian (SAS) AF: 0.0235 AC: 2019 AN: 85826

European-Finnish (FIN) AF: 0.0797 AC: 4236 AN: 53146

Middle Eastern (MID) AF: 0.127 AC: 728 AN: 5730

European-Non Finnish (NFE) AF: 0.118 AC: 130395 AN: 1107980

Other (OTH) AF: 0.135 AC: 8115 AN: 59990

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

African (AFR) AF: 0.556 AC: 23038 AN: 41450

American (AMR) AF: 0.143 AC: 2186 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4826

European-Finnish (FIN) AF: 0.0767 AC: 813 AN: 10596

Middle Eastern (MID) AF: 0.123 AC: 36 AN: 292

European-Non Finnish (NFE) AF: 0.116 AC: 7874 AN: 67990

Other (OTH) AF: 0.201 AC: 423 AN: 2106

Alfa AF: 0.161 Hom.: 5077

Bravo AF: 0.252

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SELP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.0
DANN	Benign	0.52
PhyloP100		-0.022
Mutation Taster		=99/1	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: rs6135; hg19: chr1-169566326;