6-31572294-G-A

Variant names:

• chr6-31572294-G-A
• rs1800683
• NM_000595.4:c.-162G>A

Variant summary

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

The NM_000595.4(LTA):​c.-162G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 234,314 control chromosomes in the GnomAD database, including 16,617 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 0.38 (11706 hom., cov: 33)
  • Exomes 𝑓: 0.34 (4911 hom.)
• Consequence: LTA NM_000595.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 75 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 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.-162G>A		5_prime_UTR	Exon 1 of 4	NP_000586.2
	LTA	NM_001159740.2		c.-18G>A		5_prime_UTR	Exon 1 of 4	NP_001153212.1
	LOC100287329	NR_149045.1		n.121+289C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTA	ENST00000418386.3	TSL:1 MANE Select	c.-162G>A		5_prime_UTR	Exon 1 of 4	ENSP00000413450.2
	LTA	ENST00000471842.1	TSL:2	n.1G>A		non_coding_transcript_exon	Exon 1 of 3
	LTA	ENST00000489638.5	TSL:5	n.25G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58285 AN: 151930 Hom.: 11693 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.338 AC: 27777 AN: 82266 Hom.: 4911 Cov.: 0 AF XY: 0.335 AC XY: 14380 AN XY: 42892

African (AFR) AF: 0.499 AC: 1159 AN: 2324

American (AMR) AF: 0.324 AC: 991 AN: 3056

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 688 AN: 2750

East Asian (EAS) AF: 0.397 AC: 2276 AN: 5740

South Asian (SAS) AF: 0.261 AC: 1093 AN: 4194

European-Finnish (FIN) AF: 0.322 AC: 2055 AN: 6390

Middle Eastern (MID) AF: 0.336 AC: 145 AN: 432

European-Non Finnish (NFE) AF: 0.337 AC: 17631 AN: 52330

Other (OTH) AF: 0.344 AC: 1739 AN: 5050

GnomAD4 genome AF: 0.384 AC: 58339 AN: 152048 Hom.: 11706 Cov.: 33 AF XY: 0.379 AC XY: 28197 AN XY: 74326

African (AFR) AF: 0.507 AC: 21019 AN: 41474

American (AMR) AF: 0.347 AC: 5303 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2445 AN: 5154

South Asian (SAS) AF: 0.279 AC: 1348 AN: 4824

European-Finnish (FIN) AF: 0.302 AC: 3194 AN: 10580

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23028 AN: 67942

Other (OTH) AF: 0.349 AC: 737 AN: 2110

Alfa AF: 0.358 Hom.: 15993

Bravo AF: 0.392

Asia WGS AF: 0.329 AC: 1146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		-0.21
PromoterAI		-0.032	Neutral
Mutation Taster		=300/0	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: rs1800683; hg19: chr6-31540071;