rs746868

Positions:

• chr6-31572652-C-A
• chr6-31572652-C-G
• chr6-31572652-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000595.4(LTA):​c.-9-82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 949,358 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: 𝑓 0.000014 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: LTA NM_000595.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA	NM_000595.4	c.-9-82C>A		intron_variant		ENST00000418386.3	NP_000586.2
LOC100287329	NR_149045.1	n.52G>T		non_coding_transcript_exon_variant	1/2
LTA	NM_001159740.2	c.-9-82C>A		intron_variant			NP_001153212.1
LTA	XM_047418773.1	c.-9-82C>A		intron_variant			XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3	c.-9-82C>A		intron_variant		1	NM_000595.4	ENSP00000413450	P1
	ENST00000691266.1	n.49G>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0000136 AC: 2 AN: 147240 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000249 AC: 20 AN: 802118 Hom.: 0 Cov.: 11 AF XY: 0.0000216 AC XY: 9 AN XY: 416880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000107

Gnomad4 ASJ exome AF: 0.0000522

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000304

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000220

Gnomad4 OTH exome AF: 0.0000261

GnomAD4 genome AF: 0.0000136 AC: 2 AN: 147240 Hom.: 0 Cov.: 23 AF XY: 0.0000279 AC XY: 2 AN XY: 71740

Gnomad4 AFR AF: 0.0000251

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000151

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.40

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: rs746868; hg19: chr6-31540429;