rs6130

Positions:

• chr1-169606969-G-A
• chr1-169606969-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003005.4(SELP):​c.1499C>T​(p.Ser500Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,613,328 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.121

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0068427026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.1499C>T	p.Ser500Phe	missense_variant	9/17	ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.1499C>T	p.Ser500Phe	missense_variant	9/17	1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 170 AN: 152166 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000288 AC: 72 AN: 250258 Hom.: 0 AF XY: 0.000207 AC XY: 28 AN XY: 135242

Gnomad AFR exome AF: 0.00370

Gnomad AMR exome AF: 0.000205

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000126 AC: 184 AN: 1461044 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 78 AN XY: 726786

Gnomad4 AFR exome AF: 0.00371

Gnomad4 AMR exome AF: 0.000269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000315

Gnomad4 OTH exome AF: 0.000182

GnomAD4 genome AF: 0.00111 AC: 169 AN: 152284 Hom.: 1 Cov.: 32 AF XY: 0.00125 AC XY: 93 AN XY: 74464

Gnomad4 AFR AF: 0.00400

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.00125

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000387 AC: 47

EpiCase AF: 0.0000546

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Mar 30, 2021

SELP NM_003005.3 exon 9 p.Ser500Phe (c.1499C>T): This variant has not been reported in the literature but is present in 0.3% (93/24910) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-169576207-G-A?dataset=gnomad_r2_1). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T;.;T;T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.84	T;T;D;T;D;D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.0068	T;T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.022	D;D;D;D;D;D
Sift4G	Uncertain	0.034	D;D;D;D;D;.
Vest4		0.21, 0.22, 0.24, 0.23
MVP		0.77
MPC		0.26
ClinPred		0.093	T
GERP RS		2.3
gMVP		0.29

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: rs6130; hg19: chr1-169576207; COSMIC: COSV55254023;