6-31567297-A-T

Variant names:

• chr6-31567297-A-T
• rs1121800
• ENST00000691266.2:n.199+5286T>A

Variant summary

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

The ENST00000691266.2(ENSG00000289406):​n.199+5286T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,814 control chromosomes in the GnomAD database, including 31,738 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 (31738 hom., cov: 30)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 17 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100287329	NR_149045.1	n.121+5286T>A		intron_variant	Intron 1 of 1
LTA	XM_047418773.1	c.-341-4195A>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.199+5286T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97507 AN: 151696 Hom.: 31703 Cov.: 30

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.643 AC: 97595 AN: 151814 Hom.: 31738 Cov.: 30 AF XY: 0.644 AC XY: 47744 AN XY: 74174

African (AFR) AF: 0.736 AC: 30471 AN: 41380

American (AMR) AF: 0.585 AC: 8914 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3469 AN: 5160

South Asian (SAS) AF: 0.617 AC: 2962 AN: 4800

European-Finnish (FIN) AF: 0.656 AC: 6889 AN: 10498

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

European-Non Finnish (NFE) AF: 0.601 AC: 40874 AN: 67960

Other (OTH) AF: 0.642 AC: 1354 AN: 2108

Alfa AF: 0.614 Hom.: 3609

Bravo AF: 0.641

Asia WGS AF: 0.616 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.8
DANN	Benign	0.70
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs1121800; hg19: chr6-31535074;