chr6:160585140-T>G

Variant summary

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

The ENST00000316300(LPA):c.4195A>C(p.Thr1399Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 152070 control chromosomes in the gnomAD Genomes database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 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 0.099 ( 949 hom., cov: 32)

Exomes 𝑓: 0.11 ( 1883 hom. )

Consequence

LPA
ENST00000316300 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.90

Links

LPA (HGNC:6667):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027101636).

BA1

GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPA	NM_005577.4 linkuse as main transcript	c.4195A>C	p.Thr1399Pro	missense_variant	26/39	ENST00000316300.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPA	ENST00000316300.10 linkuse as main transcript	c.4195A>C	p.Thr1399Pro	missense_variant	26/39	1	NM_005577.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0990

AC:

15048

AN:

152070

Hom.:

949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0267

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0898

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.0809

GnomAD3 exomes

AF:

0.110

AC:

27534

AN:

250654

Hom.:

1883

AF XY:

0.113

AC XY:

15278

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.0959

Gnomad ASJ exome

AF:

0.131

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.132

AC:

192617

AN:

1461350

Hom.:

13836

AF XY:

0.131

AC XY:

95584

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.0223

Gnomad4 AMR exome

AF:

0.0968

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.145

Gnomad4 OTH exome

AF:

0.118

Alfa

AF:

0.125

Hom.:

1881

Bravo

AF:

0.0931

TwinsUK

AF:

0.139

AC:

515

ALSPAC

AF:

0.153

AC:

591

ESP6500AA

AF:

0.0278

AC:

122

ESP6500EA

AF:

0.149

AC:

1281

ExAC

AF:

0.109

AC:

13205

Asia WGS

AF:

0.0450

AC:

157

AN:

3476

EpiCase

AF:

0.144

EpiControl

AF:

0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

Cadd

Benign

Dann

Benign

0.92

Eigen

Benign

0.064

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.43

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.64

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.26

Sift

Benign

0.036

Sift4G

Uncertain

0.025

Vest4

0.15

ClinPred

0.042

GERP RS

2.4

gMVP

0.65

Splicing

Find out SpliceAI 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

Computational scores

Splicing

Publications

LitVar

Other links and lift over