6-31572652-C-G

Position:

• chr6-31572652-C-G

Variant summary

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

The NM_000595.4(LTA):​c.-9-82C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 947,558 control chromosomes in the GnomAD database, including 175,748 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 0.65 (31114 hom., cov: 23)
  • Exomes 𝑓: 0.61 (144634 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.650 AC: 95588 AN: 147086 Hom.: 31077 Cov.: 23

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 0.606 AC: 484791 AN: 800352 Hom.: 144634 Cov.: 11 AF XY: 0.606 AC XY: 252163 AN XY: 415962

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.617

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.652

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.650 AC: 95677 AN: 147206 Hom.: 31114 Cov.: 23 AF XY: 0.650 AC XY: 46649 AN XY: 71798

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.651

Alfa AF: 0.464 Hom.: 1205

Bravo AF: 0.643

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.58

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;