Variant rs2729835 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032857.5(LACTB):c.1406G>A(p.Arg469Lys) variant causes a missense change. The variant allele was found at a frequency of 0.682 in 1,613,964 control chromosomes in the GnomAD database, including 378,802 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.66 ( 33366 hom., cov: 32)

Exomes 𝑓: 0.68 ( 345436 hom. )

Consequence

LACTB
NM_032857.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.59

Variant links:

Genes affected

LACTB (HGNC:16468): (lactamase beta) This gene encodes a mitochondrially-localized protein that has sequence similarity to prokaryotic beta-lactamases. Many of the residues responsible for beta-lactamase activity are not conserved in this protein, suggesting it may have a different enzymatic function. Increased expression of the related mouse gene was found to be associated with obesity. Alternative splicing results in multiple transcript variants encoding different protein isoforms. [provided by RefSeq, Dec 2013]

LACTB links:

RPS27L (HGNC:):

RPS27L 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 (MetaRNN=5.5176224E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5 linkuse as main transcript	c.1406G>A	p.Arg469Lys	missense_variant	6/6	ENST00000261893.9	NP_116246.2	P83111-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9 linkuse as main transcript	c.1406G>A	p.Arg469Lys	missense_variant	6/6	1	NM_032857.5	ENSP00000261893.4		P83111-1
RPS27L	ENST00000559763.1 linkuse as main transcript	n.95+14054C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.656

AC:

99701

AN:

152032

Hom.:

33338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.599

Gnomad AMI

AF:

0.698

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.992

Gnomad SAS

AF:

0.749

Gnomad FIN

AF:

0.672

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.680

AC:

170758

AN:

250932

Hom.:

59563

AF XY:

0.687

AC XY:

93170

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.596

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.627

Gnomad EAS exome

AF:

0.992

Gnomad SAS exome

AF:

0.739

Gnomad FIN exome

AF:

0.676

Gnomad NFE exome

AF:

0.668

Gnomad OTH exome

AF:

0.675

GnomAD4 exome

AF:

0.684

AC:

1000286

AN:

1461814

Hom.:

345436

Cov.:

AF XY:

0.686

AC XY:

498983

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.593

Gnomad4 AMR exome

AF:

0.570

Gnomad4 ASJ exome

AF:

0.633

Gnomad4 EAS exome

AF:

0.994

Gnomad4 SAS exome

AF:

0.736

Gnomad4 FIN exome

AF:

0.674

Gnomad4 NFE exome

AF:

0.679

Gnomad4 OTH exome

AF:

0.680

GnomAD4 genome

AF:

0.656

AC:

99774

AN:

152150

Hom.:

33366

Cov.:

AF XY:

0.657

AC XY:

48872

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.599

Gnomad4 AMR

AF:

0.567

Gnomad4 ASJ

AF:

0.640

Gnomad4 EAS

AF:

0.992

Gnomad4 SAS

AF:

0.747

Gnomad4 FIN

AF:

0.672

Gnomad4 NFE

AF:

0.677

Gnomad4 OTH

AF:

0.633

Alfa

AF:

0.674

Hom.:

87194

Bravo

AF:

0.648

TwinsUK

AF:

0.685

AC:

2541

ALSPAC

AF:

0.693

AC:

2672

ESP6500AA

AF:

0.606

AC:

2671

ESP6500EA

AF:

0.670

AC:

5765

ExAC

AF:

0.683

AC:

82984

Asia WGS

AF:

0.851

AC:

2958

AN:

3478

EpiCase

AF:

0.662

EpiControl

AF:

0.656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.028

MetaRNN

Benign

5.5e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.3

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.89

REVEL

Benign

0.096

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.020

MPC

0.34

ClinPred

0.0026

GERP RS

4.5

Varity_R

0.15

gMVP

0.60

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