6-31568447-A-G

Variant names:

• chr6-31568447-A-G
• rs2844484
• XM_047418773.1:c.-341-3045A>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.121+4136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,902 control chromosomes in the GnomAD database, including 31,677 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 (31677 hom., cov: 30)
• Consequence: LOC100287329 NR_149045.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 69 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=-0.79).
• 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.121+4136T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.199+4136T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97446 AN: 151784 Hom.: 31642 Cov.: 30

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.642 AC: 97534 AN: 151902 Hom.: 31677 Cov.: 30 AF XY: 0.643 AC XY: 47697 AN XY: 74224

African (AFR) AF: 0.737 AC: 30485 AN: 41390

American (AMR) AF: 0.585 AC: 8934 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1859 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3477 AN: 5176

South Asian (SAS) AF: 0.617 AC: 2972 AN: 4814

European-Finnish (FIN) AF: 0.645 AC: 6799 AN: 10540

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

European-Non Finnish (NFE) AF: 0.601 AC: 40848 AN: 67934

Other (OTH) AF: 0.641 AC: 1353 AN: 2110

Alfa AF: 0.613 Hom.: 97386

Bravo AF: 0.641

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		0.43

Splicing

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

Other links and lift over

dbSNP: rs2844484; hg19: chr6-31536224;