chr6-31572779-T-C

Position:

chr6-31572779-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein
LTA	NM_000595.4 linkuse as main transcript	c.37T>C	p.Cys13Arg	missense_variant	2/4	ENST00000418386.3	NP_000586.2
LTA	NM_001159740.2 linkuse as main transcript	c.37T>C	p.Cys13Arg	missense_variant	2/4		NP_001153212.1
LTA	XM_047418773.1 linkuse as main transcript	c.37T>C	p.Cys13Arg	missense_variant	4/6		XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LTA	ENST00000418386.3 linkuse as main transcript	c.37T>C	p.Cys13Arg	missense_variant	2/4	1	NM_000595.4	ENSP00000413450	P1
LTA	ENST00000454783.5 linkuse as main transcript	c.37T>C	p.Cys13Arg	missense_variant	2/4	2		ENSP00000403495	P1
LTA	ENST00000471842.1 linkuse as main transcript	n.199T>C		non_coding_transcript_exon_variant	2/3	2
LTA	ENST00000489638.5 linkuse as main transcript	n.79T>C		non_coding_transcript_exon_variant	2/3	5

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

GnomAD3 exomes

AF:

0.268

AC:

65640

AN:

245246

Hom.:

9119

AF XY:

0.274

AC XY:

36602

AN XY:

133738

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 SAS exome

AF:

0.326

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

Gnomad4 AFR exome

AF:

0.280

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.300

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.271

AC:

41048

AN:

151230

Hom.:

5620

Cov.:

AF XY:

0.275

AC XY:

20275

AN XY:

73826

show subpopulations

Gnomad4 AFR

AF:

0.278

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.194

Gnomad4 SAS

AF:

0.335

Gnomad4 FIN

AF:

0.341

Gnomad4 NFE

AF:

0.262

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.268

Hom.:

11585

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

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

MutationTaster

Benign

1.0

P;P

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

Varity_R

0.22

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over