ENST00000691266.2:n.200-1384G>A

Variant names:

• chr6-31562106-C-T
• rs2516390
• ENST00000691266.2:n.200-1384G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000691266.2(ENSG00000289406):​n.200-1384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 149,760 control chromosomes in the GnomAD database, including 31,221 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31221 hom., cov: 26)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 29 publications found

Genes affected

ENSG00000289406 (HGNC:):

LTA (HGNC:6709): (lymphotoxin alpha) The encoded protein, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. The protein is highly inducible, secreted, and forms heterotrimers with lymphotoxin-beta which anchor lymphotoxin-alpha to the cell surface. This protein also mediates a large variety of inflammatory, immunostimulatory, and antiviral responses, is involved in the formation of secondary lymphoid organs during development and plays a role in apoptosis. Genetic variations in this gene are associated with susceptibility to leprosy type 4, myocardial infarction, non-Hodgkin's lymphoma, and psoriatic arthritis. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100287329	NR_149045.1	n.122-1384G>A		intron_variant	Intron 1 of 1
LTA	XM_047418773.1	c.-342+837C>T		intron_variant	Intron 1 of 5		XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289406	ENST00000691266.2	n.200-1384G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 96113 AN: 149642 Hom.: 31186 Cov.: 26

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.642 AC: 96201 AN: 149760 Hom.: 31221 Cov.: 26 AF XY: 0.643 AC XY: 46860 AN XY: 72870

African (AFR) AF: 0.737 AC: 29858 AN: 40536

American (AMR) AF: 0.585 AC: 8766 AN: 14972

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1859 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3390 AN: 5046

South Asian (SAS) AF: 0.617 AC: 2930 AN: 4746

European-Finnish (FIN) AF: 0.654 AC: 6520 AN: 9972

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.601 AC: 40738 AN: 67732

Other (OTH) AF: 0.640 AC: 1333 AN: 2084

Alfa AF: 0.613 Hom.: 112434

Bravo AF: 0.641

Asia WGS AF: 0.617 AC: 2147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.48
PhyloP100		-2.8

Splicing

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

Other links and lift over

dbSNP: rs2516390; hg19: chr6-31529883;