6-31572364-A-C

Variant names:

• chr6-31572364-A-C
• rs2239704
• NM_000595.4:c.-92A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 117 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000595.4. 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.-92A>C		5_prime_UTR	Exon 1 of 4	NP_000586.2
	LTA	NM_001159740.2		c.-10+62A>C		intron	N/A	NP_001153212.1
	LOC100287329	NR_149045.1		n.121+219T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	ENST00000418386.3	TSL:1 MANE Select	c.-92A>C		5_prime_UTR	Exon 1 of 4	ENSP00000413450.2
	LTA	ENST00000454783.5	TSL:2	c.-10+62A>C		intron	N/A	ENSP00000403495.1
	LTA	ENST00000471842.1	TSL:2	n.71A>C		non_coding_transcript_exon	Exon 1 of 3

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

African (AFR) AF: 0.736 AC: 4378 AN: 5952

American (AMR) AF: 0.557 AC: 3711 AN: 6666

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 3597 AN: 6676

East Asian (EAS) AF: 0.582 AC: 8663 AN: 14888

South Asian (SAS) AF: 0.600 AC: 8871 AN: 14790

European-Finnish (FIN) AF: 0.648 AC: 8762 AN: 13530

Middle Eastern (MID) AF: 0.611 AC: 590 AN: 966

European-Non Finnish (NFE) AF: 0.590 AC: 72638 AN: 123036

Other (OTH) AF: 0.606 AC: 7462 AN: 12314

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

African (AFR) AF: 0.737 AC: 30552 AN: 41476

American (AMR) AF: 0.582 AC: 8894 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3468

East Asian (EAS) AF: 0.671 AC: 3462 AN: 5156

South Asian (SAS) AF: 0.617 AC: 2980 AN: 4826

European-Finnish (FIN) AF: 0.645 AC: 6828 AN: 10592

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40789 AN: 67926

Other (OTH) AF: 0.640 AC: 1349 AN: 2108

Alfa AF: 0.610 Hom.: 58155

Bravo AF: 0.640

Asia WGS AF: 0.617 AC: 2146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.44
PhyloP100		-0.90
PromoterAI		-0.035	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: rs2239704; hg19: chr6-31540141; COSMIC: COSV69305293; COSMIC: COSV69305293;