rs10915239

Positions:

• chr1-29197437-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016011.5(MECR):​c.831-1179G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0328 in 152,224 control chromosomes in the GnomAD database, including 121 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 0.033 (121 hom., cov: 32)
• Consequence: MECR NM_016011.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0328 (4993/152224) while in subpopulation NFE AF= 0.0508 (3455/68014). AF 95% confidence interval is 0.0494. There are 121 homozygotes in gnomad4. There are 2364 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 121 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MECR	NM_016011.5	c.831-1179G>T		intron_variant		ENST00000263702.11	NP_057095.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MECR	ENST00000263702.11	c.831-1179G>T		intron_variant		1	NM_016011.5	ENSP00000263702	P1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4993 AN: 152106 Hom.: 121 Cov.: 32

Gnomad AFR AF: 0.00865

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00891

Gnomad FIN AF: 0.0549

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0288

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

GnomAD4 genome AF: 0.0328 AC: 4993 AN: 152224 Hom.: 121 Cov.: 32 AF XY: 0.0318 AC XY: 2364 AN XY: 74424

Gnomad4 AFR AF: 0.00862

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.0549

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0285

Alfa AF: 0.0454 Hom.: 229

Bravo AF: 0.0304

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
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: rs10915239; hg19: chr1-29523949;