rs915654

Positions:

• chr6-31570720-T-A
• chr6-31570720-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047418773.1(LTA):​c.-341-772T>A 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: LTA XM_047418773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03

Genes affected

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]

ENSG00000289406 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LTA	XM_047418773.1	c.-341-772T>A		intron_variant			XP_047274729.1
LOC100287329	NR_149045.1	n.121+1863A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289406	ENST00000691266.1	n.118+1863A>T		intron_variant

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

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.415

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

Splicing

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

Publications

LitVar

Other links and lift over

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