1-169594713-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003005.4(SELP):c.2266A>C(p.Thr756Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 1,613,462 control chromosomes in the GnomAD database, including 8,585 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.074 (574 hom., cov: 33)
  • Exomes 𝑓: 0.099 (8011 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.741

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 (MetaRNN=0.0021575987).
• BP6: Variant 1-169594713-T-G is Benign according to our data. Variant chr1-169594713-T-G is described in ClinVar as [Benign]. Clinvar id is 13527.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-169594713-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.2266A>C	p.Thr756Pro	missense_variant	13/17	ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.2266A>C	p.Thr756Pro	missense_variant	13/17	1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11228 AN: 152150 Hom.: 571 Cov.: 33

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0788

GnomAD3 exomes AF: 0.0821 AC: 20598 AN: 250820 Hom.: 1069 AF XY: 0.0818 AC XY: 11088 AN XY: 135530

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.0859

Gnomad ASJ exome AF: 0.0641

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0373

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.0806

GnomAD4 exome AF: 0.0994 AC: 145263 AN: 1461194 Hom.: 8011 Cov.: 32 AF XY: 0.0974 AC XY: 70807 AN XY: 726882

Gnomad4 AFR exome AF: 0.0160

Gnomad4 AMR exome AF: 0.0866

Gnomad4 ASJ exome AF: 0.0618

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0390

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.0888

GnomAD4 genome AF: 0.0738 AC: 11237 AN: 152268 Hom.: 574 Cov.: 33 AF XY: 0.0732 AC XY: 5452 AN XY: 74456

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.0809

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0770

Alfa AF: 0.0929 Hom.: 1786

Bravo AF: 0.0700

TwinsUK AF: 0.121 AC: 447

ALSPAC AF: 0.120 AC: 463

ESP6500AA AF: 0.0225 AC: 99

ESP6500EA AF: 0.106 AC: 914

ExAC AF: 0.0820 AC: 9951

Asia WGS AF: 0.0190 AC: 65 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.100

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

SELP-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 15, 2019

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). -

SELECTIN P POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Aug 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	4.3
Dann	Benign	0.73
DEOGEN2	Benign	0.021	T;.;T;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.73	T;T;T;T;T
MetaRNN	Benign	0.0022	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	N;N;N;.;N
REVEL	Benign	0.28
Sift	Benign	0.20	T;T;T;.;T
Sift4G	Benign	0.15	T;T;T;T;T
Vest4		0.29, 0.31, 0.32, 0.28
MPC		0.18
ClinPred		0.028	T
GERP RS		-3.9
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6136; hg19: chr1-169563951; COSMIC: COSV55251781; COSMIC: COSV55251781;