6-31569829-C-T

Variant names:

• chr6-31569829-C-T
• rs2857706
• XM_047418773.1:c.-341-1663C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_149045.1(LOC100287329):​n.121+2754G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,650 control chromosomes in the GnomAD database, including 1,744 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 (1744 hom., cov: 31)
• Consequence: LOC100287329 NR_149045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_149045.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100287329	NR_149045.1		n.121+2754G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.199+2754G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22406 AN: 151538 Hom.: 1746 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.148 AC: 22415 AN: 151650 Hom.: 1744 Cov.: 31 AF XY: 0.149 AC XY: 11018 AN XY: 74036

African (AFR) AF: 0.120 AC: 4955 AN: 41338

American (AMR) AF: 0.142 AC: 2168 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3462

East Asian (EAS) AF: 0.161 AC: 830 AN: 5168

South Asian (SAS) AF: 0.248 AC: 1189 AN: 4802

European-Finnish (FIN) AF: 0.160 AC: 1665 AN: 10408

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.157 AC: 10665 AN: 67918

Other (OTH) AF: 0.170 AC: 358 AN: 2104

Alfa AF: 0.155 Hom.: 701

Bravo AF: 0.146

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	-0.91
CADD	Benign	1.5
DANN	Benign	0.35
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs2857706; hg19: chr6-31537606;