Variant chr6-31572980-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000595.4(LTA):c.152A>C(p.His51Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,611,776 control chromosomes in the GnomAD database, including 2,801 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.042 ( 188 hom., cov: 29)

Exomes 𝑓: 0.057 ( 2613 hom. )

Consequence

LTA
NM_000595.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00500

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:

LTA (HGNC:):

LTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019662678).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LTA	NM_000595.4 linkuse as main transcript	c.152A>C	p.His51Pro	missense_variant	3/4	ENST00000418386.3	NP_000586.2	P01374Q5STV3
LTA	NM_001159740.2 linkuse as main transcript	c.152A>C	p.His51Pro	missense_variant	3/4		NP_001153212.1	P01374Q5STV3
LTA	XM_047418773.1 linkuse as main transcript	c.152A>C	p.His51Pro	missense_variant	5/6		XP_047274729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LTA	ENST00000418386.3 linkuse as main transcript	c.152A>C	p.His51Pro	missense_variant	3/4	1	NM_000595.4	ENSP00000413450.2	P01374
LTA	ENST00000454783.5 linkuse as main transcript	c.152A>C	p.His51Pro	missense_variant	3/4	2		ENSP00000403495.1	P01374
LTA	ENST00000471842.1 linkuse as main transcript	n.400A>C		non_coding_transcript_exon_variant	2/3	2
LTA	ENST00000489638.5 linkuse as main transcript	n.280A>C		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.0420

AC:

6343

AN:

150884

Hom.:

189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.0177

Gnomad AMR

AF:

0.0354

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.0109

Gnomad SAS

AF:

0.0451

Gnomad FIN

AF:

0.0548

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0632

Gnomad OTH

AF:

0.0531

GnomAD3 exomes

AF:

0.0474

AC:

11706

AN:

247216

Hom.:

353

AF XY:

0.0497

AC XY:

6692

AN XY:

134582

show subpopulations

Gnomad AFR exome

AF:

0.0103

Gnomad AMR exome

AF:

0.0297

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.00957

Gnomad SAS exome

AF:

0.0514

Gnomad FIN exome

AF:

0.0547

Gnomad NFE exome

AF:

0.0637

Gnomad OTH exome

AF:

0.0488

GnomAD4 exome

AF:

0.0570

AC:

83282

AN:

1460774

Hom.:

2613

Cov.:

AF XY:

0.0572

AC XY:

41573

AN XY:

726712

show subpopulations

Gnomad4 AFR exome

AF:

0.00786

Gnomad4 AMR exome

AF:

0.0310

Gnomad4 ASJ exome

AF:

0.0254

Gnomad4 EAS exome

AF:

0.0141

Gnomad4 SAS exome

AF:

0.0537

Gnomad4 FIN exome

AF:

0.0536

Gnomad4 NFE exome

AF:

0.0626

Gnomad4 OTH exome

AF:

0.0498

GnomAD4 genome

AF:

0.0420

AC:

6345

AN:

151002

Hom.:

188

Cov.:

AF XY:

0.0420

AC XY:

3096

AN XY:

73702

show subpopulations

Gnomad4 AFR

AF:

0.0111

Gnomad4 AMR

AF:

0.0354

Gnomad4 ASJ

AF:

0.0237

Gnomad4 EAS

AF:

0.0111

Gnomad4 SAS

AF:

0.0454

Gnomad4 FIN

AF:

0.0548

Gnomad4 NFE

AF:

0.0632

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.0591

Hom.:

445

Bravo

AF:

0.0381

ESP6500AA

AF:

0.0142

AC:

ESP6500EA

AF:

0.0701

AC:

380

ExAC

AF:

0.0479

AC:

5704

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0694

EpiControl

AF:

0.0691

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.9

DANN

Benign

0.75

DEOGEN2

Benign

0.34

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.044

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.083

Sift

Benign

0.25

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;B

Vest4

0.058

MPC

1.3

ClinPred

0.0019

GERP RS

-2.8

Varity_R

0.078

gMVP

0.46

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over