Variant 6-31572536-A-G 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.-10+90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 590,314 control chromosomes in the GnomAD database, including 37,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.39 ( 11682 hom., cov: 31)

Exomes 𝑓: 0.34 ( 26251 hom. )

Consequence

LTA
NM_000595.4 intron

Scores

Clinical Significance

risk factor no assertion criteria provided O:2

Conservation

PhyloP100: -2.15

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
LTA	NM_000595.4 linkuse as main transcript	c.-10+90A>G	intron_variant	ENST00000418386.3	NP_000586.2	P01374Q5STV3
LTA	NM_001159740.2 linkuse as main transcript	c.-9-198A>G	intron_variant		NP_001153212.1	P01374Q5STV3
LTA	XM_047418773.1 linkuse as main transcript	c.-9-198A>G	intron_variant		XP_047274729.1
LOC100287329	NR_149045.1 linkuse as main transcript	n.121+47T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LTA	ENST00000418386.3 linkuse as main transcript	c.-10+90A>G		intron_variant		1	NM_000595.4	ENSP00000413450.2		P01374

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58221

AN:

151044

Hom.:

11669

Cov.:

show subpopulations

Gnomad AFR

AF:

0.509

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.354

GnomAD4 exome

AF:

0.339

AC:

149027

AN:

439150

Hom.:

26251

Cov.:

AF XY:

0.335

AC XY:

77185

AN XY:

230318

show subpopulations

Gnomad4 AFR exome

AF:

0.505

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.321

Gnomad4 NFE exome

AF:

0.337

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.386

AC:

58275

AN:

151164

Hom.:

11682

Cov.:

AF XY:

0.382

AC XY:

28191

AN XY:

73772

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.280

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.352

Alfa

AF:

0.325

Hom.:

12129

Bravo

AF:

0.393

Asia WGS

AF:

0.329

AC:

1146

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Psoriatic arthritis, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 15, 2004

- -

Myocardial infarction, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Feb 15, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.16

DANN

Benign

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over