dbSNP rs1800683: LTA:c.-162G>A (chr6-31572294-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.212

Publications

75 publications found

Variant links:

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]

LTA links:

ENSG00000289406 (HGNC:):

ENSG00000289406 links:

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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=-0.66).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
LTA	NM_000595.4 link	c.-162G>A	5_prime_UTR_variant	Exon 1 of 4	ENST00000418386.3	NP_000586.2
LTA	NM_001159740.2 link	c.-18G>A	5_prime_UTR_variant	Exon 1 of 4		NP_001153212.1
LTA	XM_047418773.1 link	c.-18G>A	5_prime_UTR_variant	Exon 3 of 6		XP_047274729.1
LOC100287329	NR_149045.1 link	n.121+289C>T	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3 link	c.-162G>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_000595.4	ENSP00000413450.2

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58285

AN:

151930

Hom.:

11693

Cov.:

show subpopulations

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.:

AF XY:

0.335

AC XY:

14380

AN XY:

42892

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

858

1715

2573

3430

4288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.384

AC:

58339

AN:

152048

Hom.:

11706

Cov.:

AF XY:

0.379

AC XY:

28197

AN XY:

74326

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23028

AN:

67942

Other (OTH)

AF:

0.349

AC:

737

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1847

3694

5540

7387

9234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.358

Hom.:

15993

Bravo

AF:

0.392

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.21

PromoterAI

-0.032

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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