rs1799964

Variant names:

• chr6-31574531-T-C
• rs1799964
• NM_000595.4:c.*838T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000595.4(LTA):​c.*838T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,164 control chromosomes in the GnomAD database, including 2,988 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 0.20 (2988 hom., cov: 30)
• Consequence: LTA NM_000595.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA	NM_000595.4	c.*838T>C		downstream_gene_variant		ENST00000418386.3	NP_000586.2
LTA	NM_001159740.2	c.*838T>C		downstream_gene_variant			NP_001153212.1
LTA	XM_047418773.1	c.*838T>C		downstream_gene_variant			XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3	c.*838T>C		downstream_gene_variant		1	NM_000595.4	ENSP00000413450.2
LTA	ENST00000454783.5	c.*838T>C		downstream_gene_variant		2		ENSP00000403495.1
LTA	ENST00000471842.1	n.*207T>C		downstream_gene_variant		2
LTA	ENST00000489638.5	n.*207T>C		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29605 AN: 151046 Hom.: 2988 Cov.: 30

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.196 AC: 29631 AN: 151164 Hom.: 2988 Cov.: 30 AF XY: 0.197 AC XY: 14541 AN XY: 73770

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.236

Alfa AF: 0.211 Hom.: 5947

Bravo AF: 0.194

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799964; hg19: chr6-31542308;