rs2729835

Variant names:

• chr15-63141567-G-A
• rs2729835
• NM_032857.5:c.1406G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-63141567-G-A
• chr15-63141567-G-C
• chr15-63141567-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (33366 hom., cov: 32)
  • Exomes 𝑓: 0.68 (345436 hom.)
• Consequence: LACTB NM_032857.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 61 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LACTB	NM_032857.5	c.1406G>A	p.Arg469Lys	missense_variant	Exon 6 of 6	ENST00000261893.9	NP_116246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.1406G>A	p.Arg469Lys	missense_variant	Exon 6 of 6	1	NM_032857.5	ENSP00000261893.4
RPS27L	ENST00000559763.1	n.95+14054C>T		intron_variant	Intron 1 of 1	3
LACTB	ENST00000559782.1	n.*221G>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99701 AN: 152032 Hom.: 33338 Cov.: 32

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

GnomAD2 exomes AF: 0.680 AC: 170758 AN: 250932 AF XY: 0.687

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 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.: 66 AF XY: 0.686 AC XY: 498983 AN XY: 727200

African (AFR) AF: 0.593 AC: 19854 AN: 33480

American (AMR) AF: 0.570 AC: 25495 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 16543 AN: 26136

East Asian (EAS) AF: 0.994 AC: 39479 AN: 39698

South Asian (SAS) AF: 0.736 AC: 63442 AN: 86256

European-Finnish (FIN) AF: 0.674 AC: 36003 AN: 53408

Middle Eastern (MID) AF: 0.586 AC: 3379 AN: 5768

European-Non Finnish (NFE) AF: 0.679 AC: 755011 AN: 1111950

Other (OTH) AF: 0.680 AC: 41080 AN: 60396

GnomAD4 genome AF: 0.656 AC: 99774 AN: 152150 Hom.: 33366 Cov.: 32 AF XY: 0.657 AC XY: 48872 AN XY: 74398

African (AFR) AF: 0.599 AC: 24854 AN: 41484

American (AMR) AF: 0.567 AC: 8678 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2223 AN: 3472

East Asian (EAS) AF: 0.992 AC: 5153 AN: 5192

South Asian (SAS) AF: 0.747 AC: 3604 AN: 4824

European-Finnish (FIN) AF: 0.672 AC: 7113 AN: 10588

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45995 AN: 67984

Other (OTH) AF: 0.633 AC: 1333 AN: 2106

Alfa AF: 0.670 Hom.: 110231

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	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.73
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.028	T
MetaRNN	Benign	5.5e-7	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.3	N
PhyloP100		3.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.096
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.34
ClinPred		0.0026	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.60
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2729835; hg19: chr15-63433766; COSMIC: COSV56056000; COSMIC: COSV56056000;