rs2972355

chr5-57491325-G-A

Variant summary

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

The ENST00000506106.1(RMEL3):n.120-2750G>A 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 0.404 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

Genes affected

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

LOC102724122 (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 = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC102724122	XR_007059132.1	n.549+2397G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMEL3	ENST00000506106.1	n.120-2750G>A		intron_variant, non_coding_transcript_variant		2
RMEL3	ENST00000664944.1	n.310+2397G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.409

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	6.6
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2972355; hg19: chr5-56787152;