rs3093546
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000595.4(LTA):c.-91G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 361,008 control chromosomes in the GnomAD database, including 290 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 0.030 ( 108 hom., cov: 32)
Exomes 𝑓: 0.035 ( 182 hom. )
Consequence
LTA
NM_000595.4 5_prime_UTR
NM_000595.4 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.60
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0304 (4634/152260) while in subpopulation NFE AF= 0.0463 (3149/68004). AF 95% confidence interval is 0.045. There are 108 homozygotes in gnomad4. There are 2176 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 108 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LTA | NM_000595.4 | c.-91G>A | 5_prime_UTR_variant | 1/4 | ENST00000418386.3 | ||
LOC100287329 | NR_149045.1 | n.121+218C>T | intron_variant, non_coding_transcript_variant | ||||
LTA | NM_001159740.2 | c.-10+63G>A | intron_variant | ||||
LTA | XM_047418773.1 | c.-10+63G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LTA | ENST00000418386.3 | c.-91G>A | 5_prime_UTR_variant | 1/4 | 1 | NM_000595.4 | P1 | ||
ENST00000691266.1 | n.118+218C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0305 AC: 4635AN: 152142Hom.: 108 Cov.: 32
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GnomAD4 exome AF: 0.0348 AC: 7267AN: 208748Hom.: 182 Cov.: 0 AF XY: 0.0336 AC XY: 3648AN XY: 108444
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GnomAD4 genome ? AF: 0.0304 AC: 4634AN: 152260Hom.: 108 Cov.: 32 AF XY: 0.0292 AC XY: 2176AN XY: 74434
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at