NM_000595.4:c.*865C>T

Variant names:

• chr6-31574558-C-T
• rs4647198
• NM_000595.4:c.*865C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000595.4(LTA):​c.*865C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 151,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0012 (0 hom., cov: 31)
• Consequence: LTA NM_000595.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 4 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA	NM_000595.4	c.*865C>T		downstream_gene_variant		ENST00000418386.3	NP_000586.2
LTA	NM_001159740.2	c.*865C>T		downstream_gene_variant			NP_001153212.1
LTA	XM_047418773.1	c.*865C>T		downstream_gene_variant			XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3	c.*865C>T		downstream_gene_variant		1	NM_000595.4	ENSP00000413450.2
LTA	ENST00000454783.5	c.*865C>T		downstream_gene_variant		2		ENSP00000403495.1
LTA	ENST00000471842.1	n.*234C>T		downstream_gene_variant		2
LTA	ENST00000489638.5	n.*234C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 151290 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000463

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00165

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000861

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00240

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

GnomAD4 genome AF: 0.00124 AC: 187 AN: 151408 Hom.: 0 Cov.: 31 AF XY: 0.00115 AC XY: 85 AN XY: 73880

African (AFR) AF: 0.000461 AC: 19 AN: 41200

American (AMR) AF: 0.00165 AC: 25 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.000861 AC: 9 AN: 10448

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00189 AC: 128 AN: 67858

Other (OTH) AF: 0.00238 AC: 5 AN: 2104

Alfa AF: 0.00131 Hom.: 1

Bravo AF: 0.00136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.11
DANN	Benign	0.72
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs4647198; hg19: chr6-31542335;