rs11899538

Variant names:

• chr2-43935027-A-G
• rs11899538
• NM_133259.4:c.2505-149T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-43935027-A-G
• chr2-43935027-A-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133259.4(LRPPRC):​c.2505-149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 591,592 control chromosomes in the GnomAD database, including 8,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1538 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6927 hom.)
• Consequence: LRPPRC NM_133259.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.226
• Publications: 2 publications found

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]

LRPPRC Gene-Disease associations (from GenCC):

• congenital lactic acidosis, Saguenay-Lac-Saint-Jean type

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• cytochrome-c oxidase deficiency disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• Leigh syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-43935027-A-G is Benign according to our data. Variant chr2-43935027-A-G is described in ClinVar as Benign. ClinVar VariationId is 676252.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133259.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPPRC	NM_133259.4	MANE Select	c.2505-149T>C		intron	N/A	NP_573566.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPPRC	ENST00000260665.12	TSL:1 MANE Select	c.2505-149T>C		intron	N/A	ENSP00000260665.7	P42704
	LRPPRC	ENST00000683125.1		c.2505-149T>C		intron	N/A	ENSP00000507939.1	A0A804HKI2
	LRPPRC	ENST00000958038.1		c.2505-149T>C		intron	N/A	ENSP00000628097.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16246 AN: 152036 Hom.: 1526 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.138 AC: 60545 AN: 439434 Hom.: 6927 AF XY: 0.142 AC XY: 32806 AN XY: 231680

African (AFR) AF: 0.0357 AC: 427 AN: 11972

American (AMR) AF: 0.216 AC: 3316 AN: 15326

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 1432 AN: 13218

East Asian (EAS) AF: 0.490 AC: 14445 AN: 29466

South Asian (SAS) AF: 0.212 AC: 7992 AN: 37770

European-Finnish (FIN) AF: 0.0831 AC: 2795 AN: 33632

Middle Eastern (MID) AF: 0.113 AC: 220 AN: 1948

European-Non Finnish (NFE) AF: 0.0987 AC: 26748 AN: 270974

Other (OTH) AF: 0.126 AC: 3170 AN: 25128

GnomAD4 genome AF: 0.107 AC: 16277 AN: 152158 Hom.: 1538 Cov.: 32 AF XY: 0.110 AC XY: 8164 AN XY: 74392

African (AFR) AF: 0.0318 AC: 1319 AN: 41524

American (AMR) AF: 0.178 AC: 2720 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3462

East Asian (EAS) AF: 0.507 AC: 2619 AN: 5164

South Asian (SAS) AF: 0.227 AC: 1093 AN: 4816

European-Finnish (FIN) AF: 0.0691 AC: 733 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7015 AN: 67984

Other (OTH) AF: 0.123 AC: 259 AN: 2112

Alfa AF: 0.105 Hom.: 222

Bravo AF: 0.113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.50
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs11899538; hg19: chr2-44162166;