6-31566093-A-G

Variant names:

• chr6-31566093-A-G
• rs2844486
• XM_047418773.1:c.-342+4824A>G

Variant summary

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

The NR_149045.1(LOC100287329):​n.122-5371T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,488 control chromosomes in the GnomAD database, including 31,662 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 (31662 hom., cov: 29)
• Consequence: LOC100287329 NR_149045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 3 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=-0.96).
• 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: 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.122-5371T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.200-5371T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97333 AN: 151370 Hom.: 31627 Cov.: 29

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.643 AC: 97421 AN: 151488 Hom.: 31662 Cov.: 29 AF XY: 0.644 AC XY: 47652 AN XY: 73982

African (AFR) AF: 0.736 AC: 30396 AN: 41272

American (AMR) AF: 0.585 AC: 8911 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3466

East Asian (EAS) AF: 0.674 AC: 3447 AN: 5112

South Asian (SAS) AF: 0.618 AC: 2969 AN: 4808

European-Finnish (FIN) AF: 0.656 AC: 6860 AN: 10460

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40832 AN: 67848

Other (OTH) AF: 0.643 AC: 1349 AN: 2098

Alfa AF: 0.612 Hom.: 3571

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	-0.96
CADD	Benign	0.96
DANN	Benign	0.19
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs2844486; hg19: chr6-31533870;