rs4953035

chr2-43916201-G-Achr2-43916201-G-C

Variant summary

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

The NM_133259.4(LRPPRC):c.3148+1824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,136 control chromosomes in the GnomAD database, including 31,823 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 0.63 (31823 hom., cov: 32)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRPPRC	NM_133259.4	c.3148+1824C>T		intron_variant		ENST00000260665.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRPPRC	ENST00000260665.12	c.3148+1824C>T		intron_variant		1	NM_133259.4	P3

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95309 AN: 152018 Hom.: 31771 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.627 AC: 95420 AN: 152136 Hom.: 31823 Cov.: 32 AF XY: 0.630 AC XY: 46840 AN XY: 74360

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.633

Alfa AF: 0.566 Hom.: 3173

Bravo AF: 0.651

Asia WGS AF: 0.774 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.8
Dann	Benign	0.47

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: rs4953035; hg19: chr2-44143340;