rs2009658

Variant names:

• chr6-31570467-C-G
• rs2009658
• ENST00000691266.2:n.199+2116G>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+2116G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,206 control chromosomes in the GnomAD database, including 1,725 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 0.15 (1725 hom., cov: 32)
• Consequence: ENSG00000289406 ENST00000691266.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 66 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 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.121+2116G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.199+2116G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22338 AN: 152088 Hom.: 1727 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.147 AC: 22346 AN: 152206 Hom.: 1725 Cov.: 32 AF XY: 0.148 AC XY: 11022 AN XY: 74428

African (AFR) AF: 0.117 AC: 4877 AN: 41524

American (AMR) AF: 0.140 AC: 2139 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3468

East Asian (EAS) AF: 0.161 AC: 834 AN: 5184

South Asian (SAS) AF: 0.247 AC: 1191 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1715 AN: 10598

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10662 AN: 68012

Other (OTH) AF: 0.163 AC: 344 AN: 2106

Alfa AF: 0.155 Hom.: 1100

Bravo AF: 0.144

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.75
PhyloP100		0.042

Splicing

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

Other links and lift over

dbSNP: rs2009658; hg19: chr6-31538244;