2-43962348-G-A

Position:

• chr2-43962348-G-A

Variant summary

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

The NM_133259.4(LRPPRC):​c.1488+1240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,016 control chromosomes in the GnomAD database, including 13,589 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 0.41 (13589 hom., cov: 32)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

Genes affected

LRPPRC (HGNC:15714): (leucine rich pentatricopeptide repeat containing) This gene encodes a leucine-rich protein that has multiple pentatricopeptide repeats (PPR). The precise role of this protein is unknown but studies suggest it may play a role in cytoskeletal organization, vesicular transport, or in transcriptional regulation of both nuclear and mitochondrial genes. The protein localizes primarily to mitochondria and is predicted to have an N-terminal mitochondrial targeting sequence. Mutations in this gene are associated with the French-Canadian type of Leigh syndrome. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRPPRC	NM_133259.4	c.1488+1240C>T		intron_variant		ENST00000260665.12	NP_573566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRPPRC	ENST00000260665.12	c.1488+1240C>T		intron_variant		1	NM_133259.4	ENSP00000260665	P3

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62417 AN: 151898 Hom.: 13578 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.411 AC: 62468 AN: 152016 Hom.: 13589 Cov.: 32 AF XY: 0.407 AC XY: 30254 AN XY: 74278

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.0407

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.395

Alfa AF: 0.457 Hom.: 10785

Bravo AF: 0.396

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.31
DANN	Benign	0.66

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: rs12712902; hg19: chr2-44189487;