Genetic Variant ENST00000691266.2:n.199+593G>A (chr6-31571990-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000691266.2(ENSG00000289406):n.199+593G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 154,464 control chromosomes in the GnomAD database, including 1,778 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 0.15 ( 1756 hom., cov: 31)

Exomes 𝑓: 0.13 ( 22 hom. )

Consequence

ENSG00000289406
ENST00000691266.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.887

Publications

64 publications found

Variant links:

COSMIC-nc: COSV69305560

Genes affected

ENSG00000289406 (HGNC:):

ENSG00000289406 links:

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]

LTA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
LOC100287329	NR_149045.1 link	n.121+593G>A	intron_variant	Intron 1 of 1
LTA	XM_047418773.1 link	c.-177-145C>T	intron_variant	Intron 2 of 5	XP_047274729.1
LTA	NM_001159740.2 link	c.-322C>T	upstream_gene_variant		NP_001153212.1	P01374Q5STV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289406	ENST00000691266.2 link	n.199+593G>A		intron_variant	Intron 1 of 1
LTA	ENST00000454783.5 link	c.-322C>T		upstream_gene_variant		2		ENSP00000403495.1		P01374

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22504

AN:

151854

Hom.:

1758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.140

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.168

GnomAD4 exome

AF:

0.134

AC:

334

AN:

2494

Hom.:

AF XY:

0.142

AC XY:

211

AN XY:

1482

show subpopulations

African (AFR)

AF:

0.0938

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0909

AC:

AN:

South Asian (SAS)

AF:

0.188

AC:

AN:

European-Finnish (FIN)

AF:

0.145

AC:

226

AN:

1564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.117

AC:

AN:

736

Other (OTH)

AF:

0.121

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.148

AC:

22513

AN:

151970

Hom.:

1756

Cov.:

AF XY:

0.149

AC XY:

11100

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.120

AC:

4987

AN:

41436

American (AMR)

AF:

0.142

AC:

2173

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

516

AN:

3470

East Asian (EAS)

AF:

0.160

AC:

825

AN:

5160

South Asian (SAS)

AF:

0.248

AC:

1190

AN:

4806

European-Finnish (FIN)

AF:

0.162

AC:

1718

AN:

10576

Middle Eastern (MID)

AF:

0.144

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.157

AC:

10679

AN:

67944

Other (OTH)

AF:

0.169

AC:

356

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

971

1942

2913

3884

4855

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.161

Hom.:

4801

Bravo

AF:

0.146

Asia WGS

AF:

0.222

AC:

773

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.0

(source)

DANN

Benign

0.76

PhyloP100

-0.89

PromoterAI

0.0036

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over