rs12046213

Variant names:

• chr1-29186811-G-A
• rs12046213
• XR_007060747.1:n.1828-55C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-29186811-G-A
• chr1-29186811-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007060747.1(MECR):​n.1828-55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,200 control chromosomes in the GnomAD database, including 1,374 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 0.12 (1374 hom., cov: 32)
• Consequence: MECR XR_007060747.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 4 publications found

Genes affected

MECR (HGNC:19691): (mitochondrial trans-2-enoyl-CoA reductase) The protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis. Defects in this gene are a cause of childhood-onset dystonia and optic atrophy. [provided by RefSeq, Mar 2017]

MECR Gene-Disease associations (from GenCC):

• dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17503 AN: 152082 Hom.: 1379 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.115 AC: 17503 AN: 152200 Hom.: 1374 Cov.: 32 AF XY: 0.122 AC XY: 9062 AN XY: 74420

African (AFR) AF: 0.108 AC: 4487 AN: 41534

American (AMR) AF: 0.144 AC: 2206 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 394 AN: 3466

East Asian (EAS) AF: 0.407 AC: 2098 AN: 5152

South Asian (SAS) AF: 0.241 AC: 1163 AN: 4828

European-Finnish (FIN) AF: 0.144 AC: 1529 AN: 10594

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5329 AN: 68012

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.0905 Hom.: 103

Bravo AF: 0.116

Asia WGS AF: 0.271 AC: 942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.4
DANN	Benign	0.55
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12046213; hg19: chr1-29513323;