1-169611647-C-T

Variant names:

• chr1-169611647-C-T
• rs6131
• NM_003005.4:c.992G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003005.4(SELP):​c.992G>A​(p.Ser331Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,613,720 control chromosomes in the GnomAD database, including 30,311 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S331G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.22 (4153 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26158 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.75
• Publications: 95 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.726286E-4).
• BP6: Variant 1-169611647-C-T is Benign according to our data. Variant chr1-169611647-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060479.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.992G>A	p.Ser331Asn	missense_variant	Exon 7 of 17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.992G>A	p.Ser331Asn	missense_variant	Exon 7 of 17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33723 AN: 151900 Hom.: 4136 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.220

GnomAD2 exomes AF: 0.198 AC: 49569 AN: 250832 AF XY: 0.201

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.0932

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.216

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.190

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.184 AC: 268245 AN: 1461702 Hom.: 26158 Cov.: 35 AF XY: 0.186 AC XY: 135318 AN XY: 727152

African (AFR) AF: 0.320 AC: 10706 AN: 33466

American (AMR) AF: 0.100 AC: 4487 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 6279 AN: 26128

East Asian (EAS) AF: 0.189 AC: 7507 AN: 39696

South Asian (SAS) AF: 0.246 AC: 21202 AN: 86252

European-Finnish (FIN) AF: 0.202 AC: 10784 AN: 53416

Middle Eastern (MID) AF: 0.211 AC: 1216 AN: 5766

European-Non Finnish (NFE) AF: 0.175 AC: 194086 AN: 1111884

Other (OTH) AF: 0.198 AC: 11978 AN: 60386

GnomAD4 genome AF: 0.222 AC: 33769 AN: 152018 Hom.: 4153 Cov.: 32 AF XY: 0.220 AC XY: 16330 AN XY: 74324

African (AFR) AF: 0.322 AC: 13337 AN: 41406

American (AMR) AF: 0.143 AC: 2185 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3464

East Asian (EAS) AF: 0.208 AC: 1077 AN: 5168

South Asian (SAS) AF: 0.246 AC: 1189 AN: 4824

European-Finnish (FIN) AF: 0.195 AC: 2055 AN: 10562

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12405 AN: 67982

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.198 Hom.: 14244

Bravo AF: 0.221

TwinsUK AF: 0.165 AC: 612

ALSPAC AF: 0.166 AC: 641

ESP6500AA AF: 0.303 AC: 1336

ESP6500EA AF: 0.188 AC: 1618

ExAC AF: 0.206 AC: 24965

Asia WGS AF: 0.240 AC: 835 AN: 3478

EpiCase AF: 0.185

EpiControl AF: 0.182

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SELP-related disorder Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	0.079
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.064
DANN	Benign	0.50
DEOGEN2	Benign	0.014	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.0022	T;T;T
MetaRNN	Benign	0.00097	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		-3.8
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.66	N;N;N
REVEL	Benign	0.011
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.46	T;T;T
Vest4		0.048, 0.054
MPC		0.055
ClinPred		0.00086	T
GERP RS		-4.5
gMVP		0.086
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6131; hg19: chr1-169580885; COSMIC: COSV55249092;