2-216028914-T-G

Position:

• chr2-216028914-T-G

Variant summary

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

The NM_001372189.1(MREG):​c.-68+5048A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,598 control chromosomes in the GnomAD database, including 36,922 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 0.70 (36922 hom., cov: 29)
• Consequence: MREG NM_001372189.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MREG	NM_001372189.1	c.-68+5048A>C		intron_variant			NP_001359118.1
MREG	NM_001372190.1	c.-68+4769A>C		intron_variant			NP_001359119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MREG	ENST00000420348.1	c.-68+3875A>C		intron_variant		4		ENSP00000404470
MREG	ENST00000424992.5	c.-68+5048A>C		intron_variant		5		ENSP00000413302
MREG	ENST00000439791.5	c.-68+4769A>C		intron_variant		4		ENSP00000411076
PECR	ENST00000442122.5	c.*440+10277A>C		intron_variant, NMD_transcript_variant		2		ENSP00000395512

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105270 AN: 151480 Hom.: 36877 Cov.: 29

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.695 AC: 105368 AN: 151598 Hom.: 36922 Cov.: 29 AF XY: 0.696 AC XY: 51574 AN XY: 74096

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.667

Alfa AF: 0.654 Hom.: 19311

Bravo AF: 0.703

Asia WGS AF: 0.660 AC: 2286 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1344694; hg19: chr2-216893637;