rs2972355

Variant names:

• chr5-57491325-G-A
• rs2972355
• ENST00000506106.1:n.120-2750G>A

Variant summary

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

The ENST00000506106.1(RMEL3):​n.120-2750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 151,868 control chromosomes in the GnomAD database, including 12,935 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 0.40 (12935 hom., cov: 32)
• Consequence: RMEL3 ENST00000506106.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 3 publications found

Genes affected

RMEL3 (HGNC:53975): (enriched in melanoma 3)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.456 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506106.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMEL3	NR_186596.1		n.73-2750G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMEL3	ENST00000506106.1	TSL:2	n.120-2750G>A		intron	N/A
	RMEL3	ENST00000664944.2		n.345+2397G>A		intron	N/A
	RMEL3	ENST00000771489.1		n.548+2397G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61365 AN: 151750 Hom.: 12921 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.404 AC: 61410 AN: 151868 Hom.: 12935 Cov.: 32 AF XY: 0.401 AC XY: 29781 AN XY: 74220

African (AFR) AF: 0.462 AC: 19124 AN: 41410

American (AMR) AF: 0.384 AC: 5862 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1545 AN: 3468

East Asian (EAS) AF: 0.0102 AC: 53 AN: 5182

South Asian (SAS) AF: 0.288 AC: 1384 AN: 4804

European-Finnish (FIN) AF: 0.439 AC: 4613 AN: 10510

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27393 AN: 67918

Other (OTH) AF: 0.409 AC: 865 AN: 2114

Alfa AF: 0.403 Hom.: 2099

Bravo AF: 0.403

Asia WGS AF: 0.152 AC: 529 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.6
DANN	Benign	0.45
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2972355;

hg19: chr5-56787152;