rs34925488

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032857.5(LACTB):c.46G>A(p.Gly16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,419,246 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 70 hom., cov: 34)

Exomes 𝑓: 0.0019 ( 60 hom. )

Consequence

LACTB
NM_032857.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.22

Publications

6 publications found

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:

LOC107984798 (HGNC:):

LOC107984798 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025365055).

BP6

Variant 15-63121917-G-A is Benign according to our data. Variant chr15-63121917-G-A is described in ClinVar as Benign. ClinVar VariationId is 776908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032857.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LACTB	NM_032857.5	MANE Select	c.46G>A	p.Gly16Arg	missense	Exon 1 of 6	NP_116246.2
LACTB	NM_171846.4		c.46G>A	p.Gly16Arg	missense	Exon 1 of 5	NP_741982.1	P83111-2
LACTB	NM_001288585.2		c.46G>A	p.Gly16Arg	missense	Exon 1 of 5	NP_001275514.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LACTB	ENST00000261893.9	TSL:1 MANE Select	c.46G>A	p.Gly16Arg	missense	Exon 1 of 6	ENSP00000261893.4	P83111-1
	LACTB	ENST00000413507.3	TSL:1	c.46G>A	p.Gly16Arg	missense	Exon 1 of 5	ENSP00000392956.2	P83111-2

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2611

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0588

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00621

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00416

AC:

358

AN:

85998

AF XY:

0.00320

show subpopulations

Gnomad AFR exome

AF:

0.0559

Gnomad AMR exome

AF:

0.00475

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000682

Gnomad OTH exome

AF:

0.00338

GnomAD4 exome

AF:

0.00192

AC:

2429

AN:

1266954

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1084

AN XY:

623506

show subpopulations

African (AFR)

AF:

0.0610

AC:

1599

AN:

26230

American (AMR)

AF:

0.00489

AC:

104

AN:

21276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19394

East Asian (EAS)

AF:

0.00

AC:

AN:

30280

South Asian (SAS)

AF:

0.000168

AC:

AN:

59588

European-Finnish (FIN)

AF:

0.0000318

AC:

AN:

31400

Middle Eastern (MID)

AF:

0.00988

AC:

AN:

4556

European-Non Finnish (NFE)

AF:

0.000412

AC:

421

AN:

1022356

Other (OTH)

AF:

0.00480

AC:

249

AN:

51874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

133

266

399

532

665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0172

AC:

2619

AN:

152292

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1214

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0588

AC:

2443

AN:

41564

American (AMR)

AF:

0.00620

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000735

AC:

AN:

68008

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

129

257

386

514

643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.0195

ESP6500AA

AF:

0.0475

AC:

130

ESP6500EA

AF:

0.000338

AC:

ExAC

AF:

0.00387

AC:

429

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0086

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.0061

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

PhyloP100

1.2

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.010

REVEL

Benign

0.061

Sift

Benign

0.48

Sift4G

Uncertain

0.038

Polyphen

0.86

Vest4

0.13

MutPred

0.23

Gain of methylation at G16 (P = 0.012)

MVP

0.44

MPC

0.40

ClinPred

0.013

GERP RS

3.1

PromoterAI

-0.012

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.065

gMVP

0.27

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over