rs915654

Variant names:

• chr6-31570720-T-A
• rs915654
• ENST00000691266.2:n.199+1863A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31570720-T-A
• chr6-31570720-T-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+1863A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,978 control chromosomes in the GnomAD database, including 12,658 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 0.40 (12658 hom., cov: 32)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03
• Publications: 42 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100287329	NR_149045.1	n.121+1863A>T		intron_variant	Intron 1 of 1
LTA	XM_047418773.1	c.-341-772T>A		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+1863A>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60716 AN: 151860 Hom.: 12650 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.400 AC: 60767 AN: 151978 Hom.: 12658 Cov.: 32 AF XY: 0.402 AC XY: 29890 AN XY: 74298

African (AFR) AF: 0.484 AC: 20062 AN: 41416

American (AMR) AF: 0.426 AC: 6500 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3470

East Asian (EAS) AF: 0.569 AC: 2952 AN: 5186

South Asian (SAS) AF: 0.447 AC: 2150 AN: 4814

European-Finnish (FIN) AF: 0.328 AC: 3467 AN: 10560

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23092 AN: 67956

Other (OTH) AF: 0.415 AC: 878 AN: 2116

Alfa AF: 0.365 Hom.: 1397

Bravo AF: 0.412

Asia WGS AF: 0.485 AC: 1689 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.058
DANN	Benign	0.096
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs915654; hg19: chr6-31538497; COSMIC: COSV69305420;