chr2-215982428-A-T

Position:

• chr2-215982428-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+13878T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,118 control chromosomes in the GnomAD database, including 2,504 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 0.17 (2504 hom., cov: 32)
• Consequence: MREG NM_018000.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MREG	NM_018000.3	c.255+13878T>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+13878T>A		intron_variant		2	NM_018000.3	ENSP00000263268	P1
MREG	ENST00000420348.1	c.93+13878T>A		intron_variant		4		ENSP00000404470
MREG	ENST00000424992.5	c.93+13878T>A		intron_variant		5		ENSP00000413302
MREG	ENST00000439791.5	c.93+13878T>A		intron_variant		4		ENSP00000411076

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26234 AN: 152002 Hom.: 2506 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.173 AC: 26245 AN: 152118 Hom.: 2504 Cov.: 32 AF XY: 0.177 AC XY: 13155 AN XY: 74348

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.165

Alfa AF: 0.166 Hom.: 275

Bravo AF: 0.171

Asia WGS AF: 0.272 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.65

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: rs3770542; hg19: chr2-216847151;