1-169728076-C-G

Position:

• chr1-169728076-C-G

Variant summary

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

The NM_000450.2(SELE):​c.1261G>C​(p.Glu421Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,612,824 control chromosomes in the GnomAD database, including 83 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 0.013 (36 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (47 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.722

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003060788).
• BP6: Variant 1-169728076-C-G is Benign according to our data. Variant chr1-169728076-C-G is described in ClinVar as [Benign]. Clinvar id is 789698.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 = 0.0126 (1920/152320) while in subpopulation AFR AF= 0.0432 (1795/41546). AF 95% confidence interval is 0.0415. There are 36 homozygotes in gnomad4. There are 907 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2	c.1261G>C	p.Glu421Gln	missense_variant	8/14	ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.1261G>C	p.Glu421Gln	missense_variant	8/14	1	NM_000450.2	ENSP00000331736	P1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1905 AN: 152202 Hom.: 36 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00608

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00324 AC: 809 AN: 249322 Hom.: 12 AF XY: 0.00235 AC XY: 316 AN XY: 134702

Gnomad AFR exome AF: 0.0446

Gnomad AMR exome AF: 0.00190

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000165

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000443

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00134 AC: 1963 AN: 1460504 Hom.: 47 Cov.: 32 AF XY: 0.00111 AC XY: 804 AN XY: 726498

Gnomad4 AFR exome AF: 0.0478

Gnomad4 AMR exome AF: 0.00255

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000252

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.0126 AC: 1920 AN: 152320 Hom.: 36 Cov.: 33 AF XY: 0.0122 AC XY: 907 AN XY: 74494

Gnomad4 AFR AF: 0.0432

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.000712 Hom.: 6

Bravo AF: 0.0149

ESP6500AA AF: 0.0404 AC: 178

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00386 AC: 469

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.18
DANN	Benign	0.36
DEOGEN2	Benign	0.015	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.060	T;T
MetaRNN	Benign	0.0031	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.061
Sift	Benign	0.29	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.33	.;B
Vest4		0.072
MVP		0.65
MPC		0.072
ClinPred		0.0081	T
GERP RS		-1.2
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs5366; hg19: chr1-169697217;