XM_047418773.1:c.-342+3768A>G

Variant names:

• chr6-31565037-A-G
• rs2857709
• XM_047418773.1:c.-342+3768A>G

Variant summary

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

The XM_047418773.1(LTA):​c.-342+3768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,236 control chromosomes in the GnomAD database, including 62,210 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 0.90 (62210 hom., cov: 31)
• Consequence: LTA XM_047418773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 19 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC100287329	NR_149045.1		n.122-4315T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000289406	ENST00000691266.2		n.200-4315T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137326 AN: 152118 Hom.: 62142 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.903 AC: 137452 AN: 152236 Hom.: 62210 Cov.: 31 AF XY: 0.905 AC XY: 67369 AN XY: 74438

African (AFR) AF: 0.950 AC: 39472 AN: 41542

American (AMR) AF: 0.924 AC: 14141 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.966 AC: 3355 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5099 AN: 5184

South Asian (SAS) AF: 0.959 AC: 4614 AN: 4812

European-Finnish (FIN) AF: 0.874 AC: 9264 AN: 10604

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58373 AN: 68006

Other (OTH) AF: 0.931 AC: 1966 AN: 2112

Alfa AF: 0.879 Hom.: 93098

Bravo AF: 0.910

Asia WGS AF: 0.969 AC: 3369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.58
PhyloP100		-0.027

Splicing

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

Other links and lift over

dbSNP: rs2857709; hg19: chr6-31532814;