Variant 1-169594713-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.741

Variant links:

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]

SELP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0974

AC XY:

70807

AN XY:

726882

show subpopulations

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.:

AF XY:

0.0732

AC XY:

5452

AN XY:

74456

show subpopulations

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:

ESP6500EA

AF:

0.106

AC:

914

ExAC

AF:

0.0820

AC:

9951

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.100

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SELP-related disorder

Benign:1

Benign, no assertion criteria provided

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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

LIST_S2

Benign

0.73

T;T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.30

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over