rs3093546

Positions:

• chr6-31572365-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• 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]

(HGNC:):

ACMG classification

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: 4635 AN: 152142 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0317

Gnomad ASJ AF: 0.0204

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0317

GnomAD4 exome AF: 0.0348 AC: 7267 AN: 208748 Hom.: 182 Cov.: 0 AF XY: 0.0336 AC XY: 3648 AN XY: 108444

Gnomad4 AFR exome AF: 0.00578

Gnomad4 AMR exome AF: 0.0246

Gnomad4 ASJ exome AF: 0.0152

Gnomad4 EAS exome AF: 0.00452

Gnomad4 SAS exome AF: 0.00889

Gnomad4 FIN exome AF: 0.0410

Gnomad4 NFE exome AF: 0.0441

Gnomad4 OTH exome AF: 0.0358

GnomAD4 genome AF: 0.0304 AC: 4634 AN: 152260 Hom.: 108 Cov.: 32 AF XY: 0.0292 AC XY: 2176 AN XY: 74434

Gnomad4 AFR AF: 0.00734

Gnomad4 AMR AF: 0.0317

Gnomad4 ASJ AF: 0.0204

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0463

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0432 Hom.: 63

Bravo AF: 0.0283

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.092
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs3093546; hg19: chr6-31540142;