chr1-169597027-A-C

Position:

• chr1-169597027-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003005.4(SELP):​c.1855T>G​(p.Ser619Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,612,984 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.011 (32 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (21 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.479

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012057096).
• BP6: Variant 1-169597027-A-C is Benign according to our data. Variant chr1-169597027-A-C is described in ClinVar as [Benign]. Clinvar id is 777955.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 = 0.0107 (1629/152320) while in subpopulation AFR AF= 0.0375 (1558/41574). AF 95% confidence interval is 0.0359. There are 32 homozygotes in gnomad4. There are 801 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.1855T>G	p.Ser619Ala	missense_variant	11/17	ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.1855T>G	p.Ser619Ala	missense_variant	11/17	1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1620 AN: 152202 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00251 AC: 629 AN: 250618 Hom.: 18 AF XY: 0.00169 AC XY: 229 AN XY: 135520

Gnomad AFR exome AF: 0.0343

Gnomad AMR exome AF: 0.00171

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000970

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.00102 AC: 1491 AN: 1460664 Hom.: 21 Cov.: 29 AF XY: 0.000849 AC XY: 617 AN XY: 726702

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.000767

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000522

Gnomad4 OTH exome AF: 0.00277

GnomAD4 genome AF: 0.0107 AC: 1629 AN: 152320 Hom.: 32 Cov.: 33 AF XY: 0.0108 AC XY: 801 AN XY: 74494

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00220 Hom.: 9

Bravo AF: 0.0120

ESP6500AA AF: 0.0365 AC: 161

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00293 AC: 356

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000110

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	0.080
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;.;T;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.38	T;T;T;T
MetaRNN	Benign	0.012	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.31	T;T;T;T
Sift4G	Benign	0.59	T;T;T;T
Vest4		0.12, 0.16, 0.17
MVP		0.80
MPC		0.068
ClinPred		0.013	T
GERP RS		2.6
gMVP		0.23

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: rs2228672; hg19: chr1-169566265;