rs2652822

Positions:

• chr15-63130573-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.1118+923T>C		intron_variant		ENST00000261893.9	NP_116246.2
LACTB	NM_171846.4	c.*919T>C		3_prime_UTR_variant	5/5		NP_741982.1
LACTB	NM_001288585.2	c.*1038T>C		3_prime_UTR_variant	5/5		NP_001275514.1
LACTB	XM_047432128.1	c.1119-413T>C		intron_variant			XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000413507.3	c.*919T>C		3_prime_UTR_variant	5/5	1		ENSP00000392956.2
LACTB	ENST00000261893.9	c.1118+923T>C		intron_variant		1	NM_032857.5	ENSP00000261893.4
RPS27L	ENST00000559763.1	n.96-4553A>G		intron_variant		3
LACTB	ENST00000559782.1	n.292+923T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 60899 AN: 151218 Hom.: 13319 Cov.: 30

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: 5 AN: 32 Hom.: 2 Cov.: 0 AF XY: 0.167 AC XY: 3 AN XY: 18

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.402 AC: 60906 AN: 151324 Hom.: 13317 Cov.: 30 AF XY: 0.396 AC XY: 29277 AN XY: 73872

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.418

Alfa AF: 0.467 Hom.: 10145

Bravo AF: 0.386

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs2652822; hg19: chr15-63422772;