Genetic Variant LACTB:c.*919T>C (chr15-63130573-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_171846.4(LACTB):c.*919T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 151,356 control chromosomes in the GnomAD database, including 13,319 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 13317 hom., cov: 30)

Exomes 𝑓: 0.16 ( 2 hom. )

Consequence

LACTB
NM_171846.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719

Publications

38 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:

RPS27L (HGNC:18476): (ribosomal protein S27 like) This gene encodes a protein sharing 96% amino acid similarity with ribosomal protein S27, which suggests the encoded protein may be a component of the 40S ribosomal subunit. [provided by RefSeq, Jul 2008]

RPS27L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.03).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_171846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LACTB	NM_032857.5	MANE Select	c.1118+923T>C	intron	N/A	NP_116246.2
LACTB	NM_171846.4		c.*919T>C	3_prime_UTR	Exon 5 of 5	NP_741982.1	P83111-2
LACTB	NM_001288585.2		c.*1038T>C	3_prime_UTR	Exon 5 of 5	NP_001275514.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LACTB	ENST00000413507.3	TSL:1	c.*919T>C	3_prime_UTR	Exon 5 of 5	ENSP00000392956.2	P83111-2
LACTB	ENST00000261893.9	TSL:1 MANE Select	c.1118+923T>C	intron	N/A	ENSP00000261893.4	P83111-1
RPS27L	ENST00000559763.1	TSL:3	n.96-4553A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

60899

AN:

151218

Hom.:

13319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.417

GnomAD4 exome

AF:

0.156

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.214

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.402

AC:

60906

AN:

151324

Hom.:

13317

Cov.:

AF XY:

0.396

AC XY:

29277

AN XY:

73872

show subpopulations

African (AFR)

AF:

0.273

AC:

11274

AN:

41270

American (AMR)

AF:

0.328

AC:

4988

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1383

AN:

3470

East Asian (EAS)

AF:

0.205

AC:

1060

AN:

5162

South Asian (SAS)

AF:

0.276

AC:

1328

AN:

4810

European-Finnish (FIN)

AF:

0.475

AC:

4854

AN:

10228

Middle Eastern (MID)

AF:

0.455

AC:

133

AN:

292

European-Non Finnish (NFE)

AF:

0.508

AC:

34466

AN:

67878

Other (OTH)

AF:

0.418

AC:

882

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

1688

3376

5065

6753

8441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.463

Hom.:

32421

Bravo

AF:

0.386

Asia WGS

AF:

0.262

AC:

911

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.6

(source)

DANN

Benign

0.70

PhyloP100

-0.72

Mutation Taster

=100/0

polymorphism (auto)

(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