1-169729506-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000450.2(SELE):c.883G>A(p.Glu295Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000888 in 1,614,110 control chromosomes in the GnomAD database, including 12 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0049 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (3 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

Genes affected

SELE (HGNC:10718): (selectin E) The protein encoded by this gene is found in cytokine-stimulated endothelial cells and is thought to be responsible for the accumulation of blood leukocytes at sites of inflammation by mediating the adhesion of cells to the vascular lining. It exhibits structural features such as the presence of lectin- and EGF-like domains followed by short consensus repeat (SCR) domains that contain 6 conserved cysteine residues. These proteins are part of the selectin family of cell adhesion molecules. Adhesion molecules participate in the interaction between leukocytes and the endothelium and appear to be involved in the pathogenesis of atherosclerosis. [provided by RefSeq, Jul 2008]

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006636083).
• BP6: Variant 1-169729506-C-T is Benign according to our data. Variant chr1-169729506-C-T is described in ClinVar as [Benign]. Clinvar id is 715852.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00493 (751/152338) while in subpopulation AFR AF= 0.017 (706/41572). AF 95% confidence interval is 0.0159. There are 9 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELE	NM_000450.2	c.883G>A	p.Glu295Lys	missense_variant	6/14	ENST00000333360.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELE	ENST00000333360.12	c.883G>A	p.Glu295Lys	missense_variant	6/14	1	NM_000450.2	P1

Frequencies

GnomAD3 genomes AF: 0.00485 AC: 738 AN: 152220 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00118 AC: 297 AN: 251004 Hom.: 3 AF XY: 0.000863 AC XY: 117 AN XY: 135630

Gnomad AFR exome AF: 0.0161

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.000467 AC: 682 AN: 1461772 Hom.: 3 Cov.: 32 AF XY: 0.000384 AC XY: 279 AN XY: 727184

Gnomad4 AFR exome AF: 0.0165

Gnomad4 AMR exome AF: 0.000783

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152338 Hom.: 9 Cov.: 32 AF XY: 0.00506 AC XY: 377 AN XY: 74486

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00583

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0152 AC: 67

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00159 AC: 193

Asia WGS AF: 0.00231 AC: 8 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	8.3
Dann	Benign	0.96
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.68	T;T;T;T;T
MetaRNN	Benign	0.0066	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.023
Sift	Benign	0.63	T;T;T;T;T
Sift4G	Benign	0.67	T;T;T;T;T
Polyphen		0.19	.;.;.;B;.
Vest4		0.12
MVP		0.62
MPC		0.064
ClinPred		0.0044	T
GERP RS		2.7
gMVP		0.51

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: rs5364; hg19: chr1-169698647; COSMIC: COSV60974731; COSMIC: COSV60974731;