dbSNP rs2972355: RMEL3:n.120-2750G>A (chr5-57491325-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.46

Publications

3 publications found

Variant links:

Genes affected

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

RMEL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMEL3	NR_186596.1 link	n.73-2750G>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
RMEL3	ENST00000506106.1 link	n.120-2750G>A	intron_variant	Intron 1 of 3	2
RMEL3	ENST00000664944.2 link	n.345+2397G>A	intron_variant	Intron 1 of 3
RMEL3	ENST00000771489.1 link	n.548+2397G>A	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61365

AN:

151750

Hom.:

12921

Cov.:

show subpopulations

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.:

AF XY:

0.401

AC XY:

29781

AN XY:

74220

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1842

3685

5527

7370

9212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

(source)

DANN

Benign

0.45

PhyloP100

1.5

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs2972355

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over