15-63127346-C-A

Position:

• chr15-63127346-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032857.5(LACTB):​c.616-7C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,531,018 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0084 (17 hom., cov: 33)
  • Exomes 𝑓: 0.00089 (14 hom.)
• Consequence: LACTB NM_032857.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.007061
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.101

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 15-63127346-C-A is Benign according to our data. Variant chr15-63127346-C-A is described in ClinVar as [Benign]. Clinvar id is 708588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00841 (1280/152120) while in subpopulation AFR AF= 0.0293 (1214/41486). AF 95% confidence interval is 0.0279. There are 17 homozygotes in gnomad4. There are 567 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LACTB	NM_032857.5	c.616-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261893.9	NP_116246.2
LACTB	NM_001288585.2	c.616-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001275514.1
LACTB	NM_171846.4	c.616-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_741982.1
LACTB	XM_047432128.1	c.616-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_047288084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LACTB	ENST00000261893.9	c.616-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032857.5	ENSP00000261893	P1
LACTB	ENST00000413507.3	c.616-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000392956
LACTB	ENST00000557972.1	c.139-7C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000454085
RPS27L	ENST00000559763.1	n.96-1326G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00842 AC: 1280 AN: 152002 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00263 AC: 534 AN: 203120 Hom.: 8 AF XY: 0.00182 AC XY: 202 AN XY: 110692

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.00166

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000462

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000650

GnomAD4 exome AF: 0.000893 AC: 1232 AN: 1378898 Hom.: 14 Cov.: 28 AF XY: 0.000781 AC XY: 533 AN XY: 682874

Gnomad4 AFR exome AF: 0.0326

Gnomad4 AMR exome AF: 0.00195

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000133

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000701

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00841 AC: 1280 AN: 152120 Hom.: 17 Cov.: 33 AF XY: 0.00762 AC XY: 567 AN XY: 74366

Gnomad4 AFR AF: 0.0293

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00443 Hom.: 4

Bravo AF: 0.0101

Asia WGS AF: 0.00145 AC: 6 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.7
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0071
dbscSNV1_RF	Benign	0.14
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: rs59027041; hg19: chr15-63419545;