6-31572294-G-T

Variant names:

• chr6-31572294-G-T
• rs1800683
• NM_000595.4:c.-162G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000595.4(LTA):​c.-162G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 82,592 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: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: LTA NM_000595.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTA	NM_000595.4	c.-162G>T		5_prime_UTR_variant	Exon 1 of 4	ENST00000418386.3	NP_000586.2
LTA	NM_001159740.2	c.-18G>T		5_prime_UTR_variant	Exon 1 of 4		NP_001153212.1
LTA	XM_047418773.1	c.-18G>T		5_prime_UTR_variant	Exon 3 of 6		XP_047274729.1
LOC100287329	NR_149045.1	n.121+289C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3	c.-162G>T		5_prime_UTR_variant	Exon 1 of 4	1	NM_000595.4	ENSP00000413450.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000121 AC: 1 AN: 82592 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 43062

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2334

American (AMR) AF: 0.000327 AC: 1 AN: 3062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2758

East Asian (EAS) AF: 0.00 AC: 0 AN: 5758

South Asian (SAS) AF: 0.00 AC: 0 AN: 4210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 434

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52550

Other (OTH) AF: 0.00 AC: 0 AN: 5074

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.87
PhyloP100		-0.21
PromoterAI		-0.017	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1800683; hg19: chr6-31540071;