1-169596008-T-C

Position:

• chr1-169596008-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_003005.4(SELP):​c.2018A>G​(p.Asn673Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,926 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.0059 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (9 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.97

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 -16 ACMG points.

• BP6: Variant 1-169596008-T-C is Benign according to our data. Variant chr1-169596008-T-C is described in ClinVar as [Benign]. Clinvar id is 782395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00595 (906/152292) while in subpopulation AFR AF= 0.0211 (877/41560). AF 95% confidence interval is 0.0199. There are 10 homozygotes in gnomad4. There are 444 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELP	NM_003005.4	c.2018A>G	p.Asn673Ser	missense_variant	12/17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.2018A>G	p.Asn673Ser	missense_variant	12/17	1	NM_003005.4	ENSP00000263686	P1

Frequencies

GnomAD3 genomes AF: 0.00595 AC: 906 AN: 152174 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00148 AC: 373 AN: 251378 Hom.: 2 AF XY: 0.000979 AC XY: 133 AN XY: 135860

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.000723

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000600 AC: 877 AN: 1461634 Hom.: 9 Cov.: 31 AF XY: 0.000487 AC XY: 354 AN XY: 727142

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.000805

Gnomad4 ASJ exome AF: 0.000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.00141

GnomAD4 genome AF: 0.00595 AC: 906 AN: 152292 Hom.: 10 Cov.: 32 AF XY: 0.00596 AC XY: 444 AN XY: 74470

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00122 Hom.: 1

Bravo AF: 0.00668

ESP6500AA AF: 0.0197 AC: 87

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00158 AC: 192

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T;.;T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.52
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.32	T;T;T;T;T
MetaRNN	Benign	0.0044	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N;N;.;N
REVEL	Benign	0.14
Sift	Benign	0.64	T;T;T;.;T
Sift4G	Benign	0.65	T;T;T;T;T
Vest4		0.14, 0.17, 0.17, 0.17
MVP		0.67
MPC		0.050
ClinPred		0.0072	T
GERP RS		4.2
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.77		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3917815; hg19: chr1-169565246; COSMIC: COSV55251401; COSMIC: COSV55251401;