1-169729301-G-T

Variant names:

• chr1-169729301-G-T
• rs79478039
• NM_000450.2:c.975C>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000450.2(SELE):​c.975C>A​(p.Phe325Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,614,124 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (32 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.100

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]

C1orf112 (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0082035065).
• BS2: High Homozygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2	c.975C>A	p.Phe325Leu	missense_variant	Exon 7 of 14	ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.975C>A	p.Phe325Leu	missense_variant	Exon 7 of 14	1	NM_000450.2	ENSP00000331736.7

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 492 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000699

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00141

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00485

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00352 AC: 884 AN: 250902 Hom.: 2 AF XY: 0.00365 AC XY: 495 AN XY: 135576

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00286

Gnomad ASJ exome AF: 0.00756

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00516

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00423

Gnomad OTH exome AF: 0.00474

GnomAD4 exome AF: 0.00402 AC: 5876 AN: 1461796 Hom.: 32 Cov.: 32 AF XY: 0.00395 AC XY: 2876 AN XY: 727192

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.00754

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00526

Gnomad4 FIN exome AF: 0.00154

Gnomad4 NFE exome AF: 0.00423

Gnomad4 OTH exome AF: 0.00422

GnomAD4 genome AF: 0.00322 AC: 491 AN: 152328 Hom.: 1 Cov.: 32 AF XY: 0.00293 AC XY: 218 AN XY: 74498

Gnomad4 AFR AF: 0.000697

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.00141

Gnomad4 NFE AF: 0.00485

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00433 Hom.: 2

Bravo AF: 0.00322

TwinsUK AF: 0.00431 AC: 16

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00488 AC: 42

ExAC AF: 0.00333 AC: 404

Asia WGS AF: 0.00173 AC: 6 AN: 3476

EpiCase AF: 0.00605

EpiControl AF: 0.00510

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Mar 30, 2021

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SELE NM_000450.2 exon 7 p.Phe325Leu (c.975C>A): This variant has not been reported in the literature and is present in 0.7% (77/10346) of Ashkenazi Jewish alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/1-169698442-G-T). This variant amino acid Leucine (Leu) is present in several species, including multiple mammals, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.95
DANN	Benign	0.86
DEOGEN2	Benign	0.060	.;T;T;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.67	T;T;T;T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.0082	T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	.;.;.;L;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D
REVEL	Benign	0.20
Sift	Benign	0.10	T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;T;T
Polyphen		0.10	.;.;.;B;.
Vest4		0.14
MutPred		0.64		.;Gain of ubiquitination at K328 (P = 0.0843);Gain of ubiquitination at K328 (P = 0.0843);Gain of ubiquitination at K328 (P = 0.0843);Gain of ubiquitination at K328 (P = 0.0843);
MVP		0.71
MPC		0.072
ClinPred		0.027	T
GERP RS		-4.1
gMVP		0.83

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: rs79478039; hg19: chr1-169698442;