dbSNP rs13358880: RMEL3:n.408+16555G>A (chr5-57513472-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.408+16555G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,110 control chromosomes in the GnomAD database, including 1,094 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 0.11 ( 1094 hom., cov: 32)

Consequence

RMEL3
ENST00000506106.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.330

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 (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RMEL3	NR_186596.1 link	n.361+16555G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
RMEL3	ENST00000506106.1 link	n.408+16555G>A	intron_variant	Intron 3 of 3	2
RMEL3	ENST00000664944.2 link	n.634+16555G>A	intron_variant	Intron 3 of 3
RMEL3	ENST00000771490.1 link	n.694+711G>A	intron_variant	Intron 5 of 5

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16602

AN:

151990

Hom.:

1093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.0527

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.00328

Gnomad SAS

AF:

0.0775

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.115

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

GnomAD4 genome

AF:

0.109

AC:

16623

AN:

152110

Hom.:

1094

Cov.:

AF XY:

0.110

AC XY:

8185

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.0504

AC:

2090

AN:

41480

American (AMR)

AF:

0.108

AC:

1650

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

584

AN:

3472

East Asian (EAS)

AF:

0.00329

AC:

AN:

5166

South Asian (SAS)

AF:

0.0776

AC:

374

AN:

4822

European-Finnish (FIN)

AF:

0.186

AC:

1962

AN:

10570

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9602

AN:

68004

Other (OTH)

AF:

0.114

AC:

240

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

743

1486

2230

2973

3716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.122

Hom.:

213

Bravo

AF:

0.104

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

4.7

(source)

DANN

Benign

0.44

PhyloP100

0.33

Splicing

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

Publications

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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