6-31565037-A-G

Position:

• chr6-31565037-A-G

Variant summary

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

The XM_047418773.1(LTA):​c.-342+3768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,236 control chromosomes in the GnomAD database, including 62,210 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 0.90 (62210 hom., cov: 31)
• Consequence: LTA XM_047418773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA	XM_047418773.1	c.-342+3768A>G		intron_variant			XP_047274729.1
LOC100287329	NR_149045.1	n.122-4315T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000289406	ENST00000691266.1	n.119-4315T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137326 AN: 152118 Hom.: 62142 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.903 AC: 137452 AN: 152236 Hom.: 62210 Cov.: 31 AF XY: 0.905 AC XY: 67369 AN XY: 74438

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.966

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.874

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.931

Alfa AF: 0.877 Hom.: 53578

Bravo AF: 0.910

Asia WGS AF: 0.969 AC: 3369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.58

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2857709; hg19: chr6-31532814;