rs1800683

Positions:

• chr6-31572294-G-A
• chr6-31572294-G-C

Variant summary

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

The NM_000595.4(LTA):​c.-162G>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 0.368 in 234,314 control chromosomes in the GnomAD database, including 16,617 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 0.38 (11706 hom., cov: 33)
  • Exomes 𝑓: 0.34 (4911 hom.)
• Consequence: LTA NM_000595.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3	c.-162G>A		5_prime_UTR_variant	1/4	1	NM_000595.4	ENSP00000413450	P1
	ENST00000691266.1	n.118+289C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58285 AN: 151930 Hom.: 11693 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.338 AC: 27777 AN: 82266 Hom.: 4911 Cov.: 0 AF XY: 0.335 AC XY: 14380 AN XY: 42892

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.324

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.384 AC: 58339 AN: 152048 Hom.: 11706 Cov.: 33 AF XY: 0.379 AC XY: 28197 AN XY: 74326

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.349

Alfa AF: 0.358 Hom.: 1927

Bravo AF: 0.392

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.92

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: rs1800683; hg19: chr6-31540071;