rs1041981

Variant summary

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

The NM_000595(LTA):c.179C>A(p.Thr60Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151122 control chromosomes in the gnomAD Genomes database, including 11454 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T60A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.38 ( 11454 hom., cov: 28)

Exomes 𝑓: 0.35 ( 15475 hom. )

Consequence

LTA
NM_000595 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 0.741

Links

LTA (HGNC:6709):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.4083595E-4).

BA1

GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LTA	NM_000595.4 linkuse as main transcript	c.179C>A	p.Thr60Asn	missense_variant	3/4	ENST00000418386.3
LTA	NM_001159740.2 linkuse as main transcript	c.179C>A	p.Thr60Asn	missense_variant	3/4
LTA	XM_047418773.1 linkuse as main transcript	c.179C>A	p.Thr60Asn	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LTA	ENST00000418386.3 linkuse as main transcript	c.179C>A	p.Thr60Asn	missense_variant	3/4	1	NM_000595.4	P1
LTA	ENST00000454783.5 linkuse as main transcript	c.179C>A	p.Thr60Asn	missense_variant	3/4	2		P1
LTA	ENST00000471842.1 linkuse as main transcript	n.427C>A		non_coding_transcript_exon_variant	2/3	2
LTA	ENST00000489638.5 linkuse as main transcript	n.307C>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57634

AN:

151122

Hom.:

11454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.341

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.350

GnomAD3 exomes

AF:

0.347

AC:

85595

AN:

246840

Hom.:

15475

AF XY:

0.339

AC XY:

45608

AN XY:

134378

show subpopulations

Gnomad AFR exome

AF:

0.501

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.498

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.351

AC:

512722

AN:

1459960

Hom.:

91986

AF XY:

0.348

AC XY:

252459

AN XY:

726340

show subpopulations

Gnomad4 AFR exome

AF:

0.508

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.313

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.352

Alfa

AF:

0.337

Hom.:

19942

Bravo

AF:

0.391

TwinsUK

AF:

0.375

AC:

1391

ALSPAC

AF:

0.379

AC:

1459

ESP6500AA

AF:

0.511

AC:

1543

ESP6500EA

AF:

0.331

AC:

1793

ExAC

AF:

0.347

AC:

41204

Asia WGS

AF:

0.329

AC:

1145

AN:

3478

EpiCase

AF:

0.318

EpiControl

AF:

0.322

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myocardial infarction, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Sep 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.42

MetaRNN

Benign

0.00044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

0.86

P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.010

N;N

REVEL

Benign

0.025

Sift

Benign

0.39

T;T

Sift4G

Uncertain

0.045

D;D

Polyphen

0.0050

B;B

Vest4

0.047

MPC

1.1

ClinPred

0.0010

GERP RS

3.1

Varity_R

0.030

gMVP

0.30

Splicing

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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over