6-31560549-G-C

Variant names:

• chr6-31560549-G-C
• rs2516479
• ENST00000691266.2:n.373C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000691266.2(ENSG00000289406):​n.373C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,126 control chromosomes in the GnomAD database, including 31,801 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 (31801 hom., cov: 32)
• Consequence: ENSG00000289406 ENST00000691266.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000691266.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100287329	NR_149045.1		n.295C>G		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.373C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97688 AN: 152008 Hom.: 31766 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.643 AC: 97776 AN: 152126 Hom.: 31801 Cov.: 32 AF XY: 0.643 AC XY: 47847 AN XY: 74358

African (AFR) AF: 0.737 AC: 30571 AN: 41502

American (AMR) AF: 0.585 AC: 8947 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3461 AN: 5154

South Asian (SAS) AF: 0.617 AC: 2981 AN: 4830

European-Finnish (FIN) AF: 0.654 AC: 6924 AN: 10584

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

European-Non Finnish (NFE) AF: 0.601 AC: 40877 AN: 67990

Other (OTH) AF: 0.640 AC: 1351 AN: 2110

Alfa AF: 0.472 Hom.: 1211

Bravo AF: 0.641

Asia WGS AF: 0.617 AC: 2149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		2.7

Splicing

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

Other links and lift over

dbSNP: rs2516479; hg19: chr6-31528326;