ENST00000691266.2:n.200-5107G>A

Variant names:

• chr6-31565829-C-T
• rs2857708
• ENST00000691266.2:n.200-5107G>A

Variant summary

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

The ENST00000691266.2(ENSG00000289406):​n.200-5107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,114 control chromosomes in the GnomAD database, including 959 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 0.10 (959 hom., cov: 31)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 30 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000691266.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100287329	NR_149045.1		n.122-5107G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.200-5107G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15835 AN: 151996 Hom.: 961 Cov.: 31

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.0826

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.104 AC: 15837 AN: 152114 Hom.: 959 Cov.: 31 AF XY: 0.103 AC XY: 7695 AN XY: 74358

African (AFR) AF: 0.0515 AC: 2136 AN: 41502

American (AMR) AF: 0.104 AC: 1589 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3464

East Asian (EAS) AF: 0.123 AC: 638 AN: 5184

South Asian (SAS) AF: 0.0825 AC: 397 AN: 4814

European-Finnish (FIN) AF: 0.137 AC: 1452 AN: 10576

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8912 AN: 67990

Other (OTH) AF: 0.114 AC: 241 AN: 2108

Alfa AF: 0.123 Hom.: 1736

Bravo AF: 0.101

Asia WGS AF: 0.104 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.65
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs2857708; hg19: chr6-31533606;