2-216005769-T-C

Variant names:

• chr2-216005769-T-C
• rs17295848
• NM_018000.3:c.95+7464A>G

Variant summary

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

The NM_018000.3(MREG):​c.95+7464A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 150,380 control chromosomes in the GnomAD database, including 2,560 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 0.11 (2560 hom., cov: 27)
• Consequence: MREG NM_018000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.870
• Publications: 0 publications found

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]

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

ACMG classification

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 = 0.34 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018000.3. 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_018000.3	MANE Select	c.95+7464A>G		intron	N/A	NP_060470.2	Q8N565-1
	MREG	NM_001372188.1		c.95+7464A>G		intron	N/A	NP_001359117.1
	MREG	NM_001372189.1		c.-67-9304A>G		intron	N/A	NP_001359118.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MREG	ENST00000263268.11	TSL:2 MANE Select	c.95+7464A>G		intron	N/A	ENSP00000263268.6	Q8N565-1
	MREG	ENST00000439791.5	TSL:4	c.-67-9304A>G		intron	N/A	ENSP00000411076.1	C9JAG4
	MREG	ENST00000424992.5	TSL:5	c.-67-9304A>G		intron	N/A	ENSP00000413302.1	C9JYV9

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16704 AN: 150268 Hom.: 2561 Cov.: 27

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0410

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0821

Gnomad FIN AF: 0.00260

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.00678

Gnomad OTH AF: 0.0853

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

GnomAD4 genome AF: 0.111 AC: 16716 AN: 150380 Hom.: 2560 Cov.: 27 AF XY: 0.109 AC XY: 8000 AN XY: 73272

African (AFR) AF: 0.345 AC: 14085 AN: 40884

American (AMR) AF: 0.0432 AC: 649 AN: 15012

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 142 AN: 3462

East Asian (EAS) AF: 0.148 AC: 758 AN: 5112

South Asian (SAS) AF: 0.0812 AC: 388 AN: 4778

European-Finnish (FIN) AF: 0.00260 AC: 26 AN: 10014

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.00678 AC: 460 AN: 67816

Other (OTH) AF: 0.0858 AC: 180 AN: 2098

Alfa AF: 0.0426 Hom.: 295

Bravo AF: 0.123

Asia WGS AF: 0.126 AC: 440 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	0.23
DANN	Benign	0.50
PhyloP100		-0.87
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: rs17295848; hg19: chr2-216870492;