rs2239704

Positions:

• chr6-31572364-A-C
• chr6-31572364-A-G
• chr6-31572364-A-T

Variant summary

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

The NM_000595.4(LTA):​c.-92A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 350,868 control chromosomes in the GnomAD database, including 67,795 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 0.64 (31643 hom., cov: 32)
  • Exomes 𝑓: 0.60 (36152 hom.)
• Consequence: LTA NM_000595.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA	NM_000595.4	c.-92A>C		5_prime_UTR_variant	1/4	ENST00000418386.3	NP_000586.2
LOC100287329	NR_149045.1	n.121+219T>G		intron_variant, non_coding_transcript_variant
LTA	NM_001159740.2	c.-10+62A>C		intron_variant			NP_001153212.1
LTA	XM_047418773.1	c.-10+62A>C		intron_variant			XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3	c.-92A>C		5_prime_UTR_variant	1/4	1	NM_000595.4	ENSP00000413450	P1
	ENST00000691266.1	n.118+219T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97428 AN: 151932 Hom.: 31607 Cov.: 32

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.597 AC: 118672 AN: 198818 Hom.: 36152 Cov.: 0 AF XY: 0.596 AC XY: 61521 AN XY: 103236

Gnomad4 AFR exome AF: 0.736

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.539

Gnomad4 EAS exome AF: 0.582

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.606

GnomAD4 genome AF: 0.641 AC: 97516 AN: 152050 Hom.: 31643 Cov.: 32 AF XY: 0.642 AC XY: 47705 AN XY: 74336

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.640

Alfa AF: 0.590 Hom.: 12448

Bravo AF: 0.640

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.44

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: rs2239704; hg19: chr6-31540141; COSMIC: COSV69305293; COSMIC: COSV69305293;