NM_000595.4:c.37T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000595.4(LTA):c.37T>C(p.Cys13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,609,528 control chromosomes in the GnomAD database, including 56,590 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.27 ( 5620 hom., cov: 28)

Exomes 𝑓: 0.26 ( 50970 hom. )

Consequence

LTA
NM_000595.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.598

Publications

176 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005508542).

BP6

Variant 6-31572779-T-C is Benign according to our data. Variant chr6-31572779-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059641.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
LTA	NM_000595.4 link	c.37T>C	p.Cys13Arg	missense_variant	Exon 2 of 4	ENST00000418386.3	NP_000586.2
LTA	NM_001159740.2 link	c.37T>C	p.Cys13Arg	missense_variant	Exon 2 of 4		NP_001153212.1
LTA	XM_047418773.1 link	c.37T>C	p.Cys13Arg	missense_variant	Exon 4 of 6		XP_047274729.1
LOC100287329	NR_149045.1 link	n.-76A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3 link	c.37T>C	p.Cys13Arg	missense_variant	Exon 2 of 4	1	NM_000595.4	ENSP00000413450.2

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41010

AN:

151112

Hom.:

5617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.277

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.194

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.303

GnomAD2 exomes

AF:

0.268

AC:

65640

AN:

245246

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.276

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.262

AC:

382238

AN:

1458298

Hom.:

50970

Cov.:

AF XY:

0.265

AC XY:

192001

AN XY:

725518

show subpopulations

African (AFR)

AF:

0.280

AC:

9370

AN:

33464

American (AMR)

AF:

0.214

AC:

9584

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

7827

AN:

26118

East Asian (EAS)

AF:

0.184

AC:

7314

AN:

39696

South Asian (SAS)

AF:

0.334

AC:

28808

AN:

86250

European-Finnish (FIN)

AF:

0.329

AC:

16645

AN:

50558

Middle Eastern (MID)

AF:

0.292

AC:

1685

AN:

5762

European-Non Finnish (NFE)

AF:

0.256

AC:

284633

AN:

1111400

Other (OTH)

AF:

0.271

AC:

16372

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

15382

30764

46145

61527

76909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9638

19276

28914

38552

48190

<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:

0.271

AC:

41048

AN:

151230

Hom.:

5620

Cov.:

AF XY:

0.275

AC XY:

20275

AN XY:

73826

show subpopulations

African (AFR)

AF:

0.278

AC:

11427

AN:

41144

American (AMR)

AF:

0.241

AC:

3674

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

1024

AN:

3470

East Asian (EAS)

AF:

0.194

AC:

981

AN:

5052

South Asian (SAS)

AF:

0.335

AC:

1593

AN:

4756

European-Finnish (FIN)

AF:

0.341

AC:

3577

AN:

10504

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17763

AN:

67774

Other (OTH)

AF:

0.301

AC:

631

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1455

2910

4365

5820

7275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.266

Hom.:

23778

Bravo

AF:

0.264

TwinsUK

AF:

0.252

AC:

936

ALSPAC

AF:

0.249

AC:

960

ESP6500AA

AF:

0.281

AC:

849

ESP6500EA

AF:

0.270

AC:

1465

ExAC

AF:

0.269

AC:

31695

Asia WGS

AF:

0.290

AC:

1007

AN:

3478

EpiCase

AF:

0.274

EpiControl

AF:

0.280

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LTA-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.3

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0068

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.81

N;N

PhyloP100

-0.60

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.037

Sift

Benign

0.78

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.0

B;B

Vest4

0.046

MPC

1.4

ClinPred

0.0021

GERP RS

1.3

PromoterAI

-0.053

Neutral

(source)

Varity_R

0.22

gMVP

0.56

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: -4

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over