1-169593666-C-T

Variant names:

• chr1-169593666-C-T
• rs6128
• NM_003005.4:c.2346G>A

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.2346G>A​(p.Thr782Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,612,630 control chromosomes in the GnomAD database, including 39,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (7892 hom., cov: 32)
  • Exomes 𝑓: 0.19 (31683 hom.)
• Consequence: SELP NM_003005.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.886

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 (REVEL=0.002).
• BP6: Variant 1-169593666-C-T is Benign according to our data. Variant chr1-169593666-C-T is described in ClinVar as [Benign]. Clinvar id is 3059830.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.886 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.2346G>A	p.Thr782Thr	synonymous_variant	Exon 14 of 17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.2346G>A	p.Thr782Thr	synonymous_variant	Exon 14 of 17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42902 AN: 151908 Hom.: 7872 Cov.: 32

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.241 AC: 60380 AN: 250966 AF XY: 0.229

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.678

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.185 AC: 270454 AN: 1460606 Hom.: 31683 Cov.: 31 AF XY: 0.183 AC XY: 132978 AN XY: 726638

Gnomad4 AFR exome AF: 0.490 AC: 16380 AN: 33436

Gnomad4 AMR exome AF: 0.259 AC: 11543 AN: 44616

Gnomad4 ASJ exome AF: 0.193 AC: 5049 AN: 26098

Gnomad4 EAS exome AF: 0.594 AC: 23550 AN: 39672

Gnomad4 SAS exome AF: 0.164 AC: 14155 AN: 86164

Gnomad4 FIN exome AF: 0.228 AC: 12189 AN: 53358

Gnomad4 NFE exome AF: 0.155 AC: 172745 AN: 1111140

Gnomad4 Remaining exome AF: 0.227 AC: 13706 AN: 60358

GnomAD4 genome AF: 0.283 AC: 42957 AN: 152024 Hom.: 7892 Cov.: 32 AF XY: 0.285 AC XY: 21207 AN XY: 74298

Gnomad4 AFR AF: 0.482 AC: 0.481521 AN: 0.481521

Gnomad4 AMR AF: 0.270 AC: 0.27024 AN: 0.27024

Gnomad4 ASJ AF: 0.190 AC: 0.190023 AN: 0.190023

Gnomad4 EAS AF: 0.649 AC: 0.64917 AN: 0.64917

Gnomad4 SAS AF: 0.184 AC: 0.183839 AN: 0.183839

Gnomad4 FIN AF: 0.230 AC: 0.230297 AN: 0.230297

Gnomad4 NFE AF: 0.159 AC: 0.159457 AN: 0.159457

Gnomad4 OTH AF: 0.270 AC: 0.269668 AN: 0.269668

Alfa AF: 0.190 Hom.: 4405

Bravo AF: 0.299

Asia WGS AF: 0.442 AC: 1535 AN: 3478

EpiCase AF: 0.157

EpiControl AF: 0.159

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SELP-related disorder Benign:1

Oct 21, 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	-0.83
CADD	Benign	0.69
DANN	Benign	0.37
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

Publications

LitVar

Other links and lift over

dbSNP: rs6128; hg19: chr1-169562904; COSMIC: COSV55252508; COSMIC: COSV55252508;