chr1-169597075-C-T

Variant names:

• chr1-169597075-C-T
• rs6127
• NM_003005.4:c.1807G>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.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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.67 (35072 hom., cov: 32)
  • Exomes 𝑓: 0.59 (256126 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.410
• Publications: 57 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=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 VariationId is 3059039.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003005.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	NM_003005.4	MANE Select	c.1807G>A	p.Asp603Asn	missense	Exon 11 of 17	NP_002996.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	ENST00000263686.11	TSL:1 MANE Select	c.1807G>A	p.Asp603Asn	missense	Exon 11 of 17	ENSP00000263686.5
	SELP	ENST00000426706.6	TSL:1	c.1804G>A	p.Asp602Asn	missense	Exon 10 of 15	ENSP00000391694.2
	SELP	ENST00000367786.6	TSL:5	c.1621G>A	p.Asp541Asn	missense	Exon 10 of 16	ENSP00000356760.1

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

GnomAD2 exomes AF: 0.645 AC: 160192 AN: 248338 AF XY: 0.630

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 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

African (AFR) AF: 0.833 AC: 27418 AN: 32900

American (AMR) AF: 0.763 AC: 33827 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 15325 AN: 25932

East Asian (EAS) AF: 0.956 AC: 37926 AN: 39690

South Asian (SAS) AF: 0.564 AC: 48343 AN: 85772

European-Finnish (FIN) AF: 0.645 AC: 34324 AN: 53200

Middle Eastern (MID) AF: 0.538 AC: 3085 AN: 5734

European-Non Finnish (NFE) AF: 0.556 AC: 616361 AN: 1108672

Other (OTH) AF: 0.609 AC: 36554 AN: 60056

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

African (AFR) AF: 0.823 AC: 34075 AN: 41422

American (AMR) AF: 0.701 AC: 10703 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2069 AN: 3466

East Asian (EAS) AF: 0.963 AC: 4986 AN: 5178

South Asian (SAS) AF: 0.592 AC: 2851 AN: 4814

European-Finnish (FIN) AF: 0.646 AC: 6832 AN: 10570

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37958 AN: 67968

Other (OTH) AF: 0.662 AC: 1395 AN: 2106

Alfa AF: 0.602 Hom.: 126213

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: no assertion criteria provided

Submissions by phenotype

SELP-related disorder Benign:1

Oct 17, 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 v4.9

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
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.036	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.41
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.071
Sift	Benign	0.91	T
Sift4G	Benign	0.69	T
Vest4		0.063
MPC		0.056
ClinPred		0.00083	T
GERP RS		-1.8
gMVP		0.081
Mutation Taster		=100/0	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: rs6127; hg19: chr1-169566313; COSMIC: COSV107225266;