chr6-31563438-T-G

Variant names:

• chr6-31563438-T-G
• rs928815
• ENST00000691266.2:n.200-2716A>C

Variant summary

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

The ENST00000691266.2(ENSG00000289406):​n.200-2716A>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 151,936 control chromosomes in the GnomAD database, including 31,778 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 (31778 hom., cov: 30)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• Publications: 38 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 = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100287329	NR_149045.1	n.122-2716A>C		intron_variant	Intron 1 of 1
LTA	XM_047418773.1	c.-342+2169T>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.200-2716A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97623 AN: 151818 Hom.: 31743 Cov.: 30

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.602

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: 97711 AN: 151936 Hom.: 31778 Cov.: 30 AF XY: 0.644 AC XY: 47822 AN XY: 74252

African (AFR) AF: 0.736 AC: 30516 AN: 41440

American (AMR) AF: 0.586 AC: 8928 AN: 15240

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

East Asian (EAS) AF: 0.672 AC: 3472 AN: 5170

South Asian (SAS) AF: 0.617 AC: 2970 AN: 4812

European-Finnish (FIN) AF: 0.657 AC: 6921 AN: 10538

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

European-Non Finnish (NFE) AF: 0.602 AC: 40886 AN: 67954

Other (OTH) AF: 0.642 AC: 1356 AN: 2112

Alfa AF: 0.616 Hom.: 92827

Bravo AF: 0.641

Asia WGS AF: 0.617 AC: 2149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.75
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs928815; hg19: chr6-31531215;