chr6-31569019-T-G

Variant names:

• chr6-31569019-T-G
• rs2844483
• ENST00000691266.2:n.199+3564A>C

Variant summary

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

The ENST00000691266.2(ENSG00000289406):​n.199+3564A>C 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 151,870 control chromosomes in the GnomAD database, including 31,746 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 (31746 hom., cov: 31)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 6 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=-0.88).
• 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.121+3564A>C		intron_variant	Intron 1 of 1
LTA	XM_047418773.1	c.-341-2473T>G		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+3564A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97561 AN: 151752 Hom.: 31711 Cov.: 31

Gnomad AFR AF: 0.737

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: 0.643

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

GnomAD4 genome AF: 0.643 AC: 97649 AN: 151870 Hom.: 31746 Cov.: 31 AF XY: 0.644 AC XY: 47782 AN XY: 74214

African (AFR) AF: 0.737 AC: 30495 AN: 41384

American (AMR) AF: 0.585 AC: 8926 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1858 AN: 3470

East Asian (EAS) AF: 0.672 AC: 3468 AN: 5158

South Asian (SAS) AF: 0.617 AC: 2967 AN: 4810

European-Finnish (FIN) AF: 0.656 AC: 6921 AN: 10550

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

European-Non Finnish (NFE) AF: 0.601 AC: 40859 AN: 67936

Other (OTH) AF: 0.640 AC: 1348 AN: 2106

Alfa AF: 0.614 Hom.: 3609

Bravo AF: 0.641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.62
PhyloP100		1.6

Splicing

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

Other links and lift over

dbSNP: rs2844483; hg19: chr6-31536796;