2-216005769-T-C

Position:

• chr2-216005769-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MREG	NM_018000.3	c.95+7464A>G		intron_variant		ENST00000263268.11	NP_060470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MREG	ENST00000263268.11	c.95+7464A>G		intron_variant		2	NM_018000.3	ENSP00000263268	P1

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.0432

Gnomad4 ASJ AF: 0.0410

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0812

Gnomad4 FIN AF: 0.00260

Gnomad4 NFE AF: 0.00678

Gnomad4 OTH AF: 0.0858

Alfa AF: 0.0409 Hom.: 164

Bravo AF: 0.123

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.50

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: rs17295848; hg19: chr2-216870492;