Genetic Variant MREG:c.-68+5048A>C (chr2-216028914-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001372189.1(MREG):c.-68+5048A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,598 control chromosomes in the GnomAD database, including 36,922 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 0.70 ( 36922 hom., cov: 29)

Consequence

MREG
NM_001372189.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

25 publications found

Variant links:

Genes affected

MREG (HGNC:25478): (melanoregulin) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in melanocyte differentiation; melanosome transport; and phagosome maturation. Predicted to act upstream of or within developmental pigmentation. Predicted to be located in late endosome membrane and melanosome membrane. Predicted to be intrinsic component of organelle membrane. Predicted to be part of protein-containing complex. Predicted to be active in melanosome. [provided by Alliance of Genome Resources, Apr 2022]

MREG links:

PECR (HGNC:18281): (peroxisomal trans-2-enoyl-CoA reductase) Enables signaling receptor binding activity and trans-2-enoyl-CoA reductase (NADPH) activity. Involved in phytol metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

PECR Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

PECR links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
MREG	NM_001372189.1 link	c.-68+5048A>C	intron_variant	Intron 1 of 4	NP_001359118.1
MREG	NM_001372190.1 link	c.-68+4769A>C	intron_variant	Intron 1 of 4	NP_001359119.1
PECR	XR_001738847.3 link	n.*174A>C	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
MREG	ENST00000439791.5 link	c.-68+4769A>C	intron_variant	Intron 1 of 4	4	ENSP00000411076.1
MREG	ENST00000424992.5 link	c.-68+5048A>C	intron_variant	Intron 1 of 4	5	ENSP00000413302.1
MREG	ENST00000420348.1 link	c.-68+3875A>C	intron_variant	Intron 1 of 3	4	ENSP00000404470.1
PECR	ENST00000442122.5 link	n.*440+10277A>C	intron_variant	Intron 7 of 7	2	ENSP00000395512.1

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105270

AN:

151480

Hom.:

36877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.615

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.622

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.651

Gnomad OTH

AF:

0.668

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

GnomAD4 genome

AF:

0.695

AC:

105368

AN:

151598

Hom.:

36922

Cov.:

AF XY:

0.696

AC XY:

51574

AN XY:

74096

show subpopulations

African (AFR)

AF:

0.770

AC:

31827

AN:

41324

American (AMR)

AF:

0.719

AC:

10951

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

2132

AN:

3466

East Asian (EAS)

AF:

0.693

AC:

3584

AN:

5170

South Asian (SAS)

AF:

0.622

AC:

2987

AN:

4800

European-Finnish (FIN)

AF:

0.730

AC:

7628

AN:

10450

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.651

AC:

44199

AN:

67860

Other (OTH)

AF:

0.667

AC:

1401

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1601

3202

4803

6404

8005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.656

Hom.:

24723

Bravo

AF:

0.703

Asia WGS

AF:

0.660

AC:

2286

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.41

(source)

DANN

Benign

0.19

PhyloP100

-1.2

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over