NM_000450.2:c.1260C>T

Variant names:

• chr1-169728077-G-A
• rs5365
• NM_000450.2:c.1260C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000450.2(SELE):​c.1260C>T​(p.Asn420Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,612,778 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (91 hom.)
• Consequence: SELE NM_000450.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-169728077-G-A is Benign according to our data. Variant chr1-169728077-G-A is described in ClinVar as Benign. ClinVar VariationId is 711295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000450.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	NM_000450.2	MANE Select	c.1260C>T	p.Asn420Asn	synonymous	Exon 8 of 14	NP_000441.2	P16581

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	ENST00000333360.12	TSL:1 MANE Select	c.1260C>T	p.Asn420Asn	synonymous	Exon 8 of 14	ENSP00000331736.7	P16581
	SELE	ENST00000367777.5	TSL:5	c.1260C>T	p.Asn420Asn	synonymous	Exon 7 of 12	ENSP00000356751.1	Q5TI74
	SELE	ENST00000367776.5	TSL:5	c.1091-150C>T		intron	N/A	ENSP00000356750.1	Q5TI73

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2791 AN: 152144 Hom.: 81 Cov.: 33

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0119

GnomAD2 exomes AF: 0.00493 AC: 1229 AN: 249318 AF XY: 0.00365

Gnomad AFR exome AF: 0.0664

Gnomad AMR exome AF: 0.00322

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00192 AC: 2801 AN: 1460516 Hom.: 91 Cov.: 32 AF XY: 0.00166 AC XY: 1209 AN XY: 726522

African (AFR) AF: 0.0657 AC: 2191 AN: 33336

American (AMR) AF: 0.00350 AC: 155 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39694

South Asian (SAS) AF: 0.000151 AC: 13 AN: 85930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5756

European-Non Finnish (NFE) AF: 0.000152 AC: 169 AN: 1111672

Other (OTH) AF: 0.00416 AC: 251 AN: 60326

GnomAD4 genome AF: 0.0184 AC: 2799 AN: 152262 Hom.: 81 Cov.: 33 AF XY: 0.0176 AC XY: 1314 AN XY: 74454

African (AFR) AF: 0.0641 AC: 2663 AN: 41530

American (AMR) AF: 0.00647 AC: 99 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68030

Other (OTH) AF: 0.0118 AC: 25 AN: 2116

Alfa AF: 0.0107 Hom.: 36

Bravo AF: 0.0202

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.38
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.26		Position offset: -19

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

Other links and lift over

dbSNP: rs5365; hg19: chr1-169697218;