rs2220846

Positions:

• chr5-57479107-T-C

Variant summary

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

The ENST00000506106.1(RMEL3):​n.120-14968T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 152,020 control chromosomes in the GnomAD database, including 12,221 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 0.39 (12221 hom., cov: 32)
• Consequence: RMEL3 ENST00000506106.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RMEL3	ENST00000506106.1	n.120-14968T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59896 AN: 151904 Hom.: 12191 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.394 AC: 59967 AN: 152020 Hom.: 12221 Cov.: 32 AF XY: 0.396 AC XY: 29402 AN XY: 74302

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.411

Alfa AF: 0.394 Hom.: 1764

Bravo AF: 0.387

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2220846; hg19: chr5-56774934;