1-169597075-C-T

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.1807G>A(p.Asp603Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 1,608,272 control chromosomes in the GnomAD database, including 291,198 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 0.67 (35072 hom., cov: 32)
  • Exomes 𝑓: 0.59 (256126 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410

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=1.1658593E-6).
• BP6: Variant 1-169597075-C-T is Benign according to our data. Variant chr1-169597075-C-T is described in ClinVar as [Benign]. Clinvar id is 3059039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.1807G>A	p.Asp603Asn	missense_variant	11/17	ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.1807G>A	p.Asp603Asn	missense_variant	11/17	1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101252 AN: 151886 Hom.: 35018 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.662

GnomAD3 exomes AF: 0.645 AC: 160192 AN: 248338 Hom.: 54236 AF XY: 0.630 AC XY: 84620 AN XY: 134278

Gnomad AFR exome AF: 0.832

Gnomad AMR exome AF: 0.771

Gnomad ASJ exome AF: 0.591

Gnomad EAS exome AF: 0.969

Gnomad SAS exome AF: 0.565

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.557

Gnomad OTH exome AF: 0.605

GnomAD4 exome AF: 0.586 AC: 853163 AN: 1456268 Hom.: 256126 Cov.: 47 AF XY: 0.583 AC XY: 422634 AN XY: 724440

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.956

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.645

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.609

GnomAD4 genome AF: 0.667 AC: 101368 AN: 152004 Hom.: 35072 Cov.: 32 AF XY: 0.672 AC XY: 49921 AN XY: 74314

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.662

Alfa AF: 0.591 Hom.: 58653

Bravo AF: 0.683

TwinsUK AF: 0.561 AC: 2082

ALSPAC AF: 0.559 AC: 2156

ESP6500AA AF: 0.815 AC: 3593

ESP6500EA AF: 0.558 AC: 4802

ExAC AF: 0.638 AC: 77513

Asia WGS AF: 0.795 AC: 2764 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

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

Oct 17, 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). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	3.2
Dann	Benign	0.22
DEOGEN2	Benign	0.0059	T;.;T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.036	T;T;T;T
MetaRNN	Benign	0.0000012	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.30	N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.91	T;T;T;T
Sift4G	Benign	0.69	T;T;T;T
Vest4		0.063, 0.062, 0.047
MPC		0.056
ClinPred		0.00083	T
GERP RS		-1.8
gMVP		0.081

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: rs6127; hg19: chr1-169566313;