6-31563533-T-G

Variant names:

• chr6-31563533-T-G
• rs7762619
• ENST00000691266.2:n.200-2811A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000691266.2(ENSG00000289406):​n.200-2811A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 152,306 control chromosomes in the GnomAD database, including 30 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 0.015 (30 hom., cov: 31)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 16 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=-0.8).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0148 (2260/152306) while in subpopulation AMR AF = 0.0241 (369/15298). AF 95% confidence interval is 0.0221. There are 30 homozygotes in GnomAd4. There are 1078 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100287329	NR_149045.1	n.122-2811A>C		intron_variant	Intron 1 of 1
LTA	XM_047418773.1	c.-342+2264T>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.200-2811A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2245 AN: 152188 Hom.: 30 Cov.: 31

Gnomad AFR AF: 0.0207

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0242

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00211

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0148 AC: 2260 AN: 152306 Hom.: 30 Cov.: 31 AF XY: 0.0145 AC XY: 1078 AN XY: 74472

African (AFR) AF: 0.0210 AC: 871 AN: 41562

American (AMR) AF: 0.0241 AC: 369 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 41 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5194

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0130 AC: 887 AN: 68032

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0133 Hom.: 80

Bravo AF: 0.0166

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.81
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs7762619; hg19: chr6-31531310;