6-31572652-C-G

Variant names:

• chr6-31572652-C-G
• rs746868
• NM_000595.4:c.-9-82C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418386.3(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 ENST00000418386.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 47 publications found

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]

ENSG00000289406 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000418386.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	NM_000595.4	MANE Select	c.-9-82C>G		intron	N/A	NP_000586.2
	LOC100287329	NR_149045.1		n.52G>C		non_coding_transcript_exon	Exon 1 of 2
	LTA	NM_001159740.2		c.-9-82C>G		intron	N/A	NP_001153212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	ENST00000418386.3	TSL:1 MANE Select	c.-9-82C>G		intron	N/A	ENSP00000413450.2
	ENSG00000289406	ENST00000691266.2		n.130G>C		non_coding_transcript_exon	Exon 1 of 2
	LTA	ENST00000454783.5	TSL:2	c.-9-82C>G		intron	N/A	ENSP00000403495.1

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

African (AFR) AF: 0.739 AC: 15295 AN: 20684

American (AMR) AF: 0.560 AC: 20796 AN: 37154

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 10617 AN: 19152

East Asian (EAS) AF: 0.617 AC: 22113 AN: 35864

South Asian (SAS) AF: 0.636 AC: 41763 AN: 65664

European-Finnish (FIN) AF: 0.652 AC: 23323 AN: 35778

Middle Eastern (MID) AF: 0.651 AC: 2840 AN: 4362

European-Non Finnish (NFE) AF: 0.597 AC: 324371 AN: 543414

Other (OTH) AF: 0.618 AC: 23673 AN: 38280

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

African (AFR) AF: 0.745 AC: 29736 AN: 39928

American (AMR) AF: 0.592 AC: 8809 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1851 AN: 3380

East Asian (EAS) AF: 0.686 AC: 3321 AN: 4842

South Asian (SAS) AF: 0.647 AC: 2958 AN: 4572

European-Finnish (FIN) AF: 0.646 AC: 6555 AN: 10140

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.609 AC: 40330 AN: 66246

Other (OTH) AF: 0.651 AC: 1322 AN: 2030

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.58
PhyloP100		0.12
PromoterAI		-0.0063	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs746868; hg19: chr6-31540429;