chr2-215995827-A-T

Position:

• chr2-215995827-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018000.3(MREG):​c.255+479T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,856 control chromosomes in the GnomAD database, including 9,552 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 0.35 (9552 hom., cov: 31)
• Consequence: MREG NM_018000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MREG	NM_018000.3	c.255+479T>A		intron_variant		ENST00000263268.11	NP_060470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MREG	ENST00000263268.11	c.255+479T>A		intron_variant		2	NM_018000.3	ENSP00000263268.6
MREG	ENST00000439791.5	c.93+479T>A		intron_variant		4		ENSP00000411076.1
MREG	ENST00000424992.5	c.93+479T>A		intron_variant		5		ENSP00000413302.1
MREG	ENST00000420348.1	c.93+479T>A		intron_variant		4		ENSP00000404470.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52765 AN: 151738 Hom.: 9536 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.348 AC: 52824 AN: 151856 Hom.: 9552 Cov.: 31 AF XY: 0.350 AC XY: 25981 AN XY: 74204

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.333

Alfa AF: 0.334 Hom.: 1081

Bravo AF: 0.353

Asia WGS AF: 0.308 AC: 1068 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.28

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: rs3770549; hg19: chr2-216860550;