rs3917724

chr1-169612357-G-A

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.821C>T(p.Thr274Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,614,082 control chromosomes in the GnomAD database, including 377 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 0.026 (212 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (165 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.383

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=0.005010903).
• BP6: Variant 1-169612357-G-A is Benign according to our data. Variant chr1-169612357-G-A is described in ClinVar as [Benign]. Clinvar id is 780277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.821C>T	p.Thr274Ile	missense_variant	6/17	ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.821C>T	p.Thr274Ile	missense_variant	6/17	1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 4000 AN: 152150 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.00706 AC: 1773 AN: 251222 Hom.: 86 AF XY: 0.00512 AC XY: 695 AN XY: 135758

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.00501

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00267 AC: 3897 AN: 1461814 Hom.: 165 Cov.: 31 AF XY: 0.00227 AC XY: 1651 AN XY: 727204

Gnomad4 AFR exome AF: 0.0946

Gnomad4 AMR exome AF: 0.00582

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000277

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.00604

GnomAD4 genome AF: 0.0263 AC: 4005 AN: 152268 Hom.: 212 Cov.: 32 AF XY: 0.0248 AC XY: 1849 AN XY: 74460

Gnomad4 AFR AF: 0.0910

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.00501 Hom.: 67

Bravo AF: 0.0304

ESP6500AA AF: 0.0917 AC: 404

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00827 AC: 1004

Asia WGS AF: 0.00693 AC: 26 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	13
Dann	Benign	0.92
DEOGEN2	Benign	0.020	T;.;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.56	T;T;T;T;T
MetaRNN	Benign	0.0050	T;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	0.25	T
PROVEAN	Benign	-1.9	N;N;N;.;N
REVEL	Benign	0.11
Sift	Benign	0.13	T;T;T;.;T
Sift4G	Benign	0.21	T;T;T;T;.
Vest4		0.087, 0.15, 0.15
MVP		0.19
MPC		0.063
ClinPred		0.0039	T
GERP RS		-8.5
gMVP		0.22

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: rs3917724; hg19: chr1-169581595; COSMIC: COSV99057165;