2-215974097-A-G

Variant names:

• chr2-215974097-A-G
• rs3770536
• NM_018000.3:c.255+22209T>C

Variant summary

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

The NM_018000.3(MREG):​c.255+22209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,052 control chromosomes in the GnomAD database, including 27,331 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 0.59 (27331 hom., cov: 32)
• Consequence: MREG NM_018000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MREG	NM_018000.3	c.255+22209T>C		intron_variant	Intron 2 of 4	ENST00000263268.11	NP_060470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MREG	ENST00000263268.11	c.255+22209T>C		intron_variant	Intron 2 of 4	2	NM_018000.3	ENSP00000263268.6
MREG	ENST00000439791.5	c.93+22209T>C		intron_variant	Intron 2 of 4	4		ENSP00000411076.1
MREG	ENST00000424992.5	c.93+22209T>C		intron_variant	Intron 2 of 4	5		ENSP00000413302.1
MREG	ENST00000420348.1	c.93+22209T>C		intron_variant	Intron 2 of 3	4		ENSP00000404470.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90204 AN: 151934 Hom.: 27319 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.594 AC: 90262 AN: 152052 Hom.: 27331 Cov.: 32 AF XY: 0.599 AC XY: 44521 AN XY: 74336

African (AFR) AF: 0.488 AC: 20216 AN: 41434

American (AMR) AF: 0.685 AC: 10462 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4253 AN: 5182

South Asian (SAS) AF: 0.491 AC: 2365 AN: 4818

European-Finnish (FIN) AF: 0.722 AC: 7644 AN: 10592

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41302 AN: 67976

Other (OTH) AF: 0.599 AC: 1261 AN: 2106

Alfa AF: 0.602 Hom.: 81774

Bravo AF: 0.593

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		-0.081
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: rs3770536; hg19: chr2-216838820;