dbSNP rs7590720: MREG:c.-68+27C>T (chr2-216033935-G-A) – 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+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,104 control chromosomes in the GnomAD database, including 40,053 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 0.72 ( 40052 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

MREG
NM_001372189.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.649

Publications

50 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:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372189.1. 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
	MREG	NM_001372189.1		c.-68+27C>T		intron	N/A	NP_001359118.1
	MREG	NM_001372190.1		c.-320C>T		upstream_gene	N/A	NP_001359119.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MREG	ENST00000424992.5	TSL:5	c.-68+27C>T	intron	N/A	ENSP00000413302.1	C9JYV9
PECR	ENST00000442122.5	TSL:2	n.*440+5256C>T	intron	N/A	ENSP00000395512.1	B4DJS2
MREG	ENST00000439791.5	TSL:4	c.-320C>T	upstream_gene	N/A	ENSP00000411076.1	C9JAG4

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

110055

AN:

151984

Hom.:

40006

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.528

Gnomad AMR

AF:

0.755

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.692

Gnomad SAS

AF:

0.640

Gnomad FIN

AF:

0.760

Gnomad MID

AF:

0.675

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.697

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.724

AC:

110157

AN:

152102

Hom.:

40052

Cov.:

AF XY:

0.724

AC XY:

53830

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.773

AC:

32080

AN:

41484

American (AMR)

AF:

0.756

AC:

11556

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2214

AN:

3472

East Asian (EAS)

AF:

0.692

AC:

3579

AN:

5170

South Asian (SAS)

AF:

0.641

AC:

3090

AN:

4824

European-Finnish (FIN)

AF:

0.760

AC:

8043

AN:

10576

Middle Eastern (MID)

AF:

0.678

AC:

198

AN:

292

European-Non Finnish (NFE)

AF:

0.698

AC:

47449

AN:

67978

Other (OTH)

AF:

0.696

AC:

1469

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1567

3134

4701

6268

7835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.705

Hom.:

137351

Bravo

AF:

0.731

Asia WGS

AF:

0.668

AC:

2326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.53

(source)

DANN

Benign

0.71

PhyloP100

-0.65

PromoterAI

-0.013

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over