Genetic Variant RBM17:c.506-148A>C (chr10-6108538-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032905.5(RBM17):c.506-148A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 555,128 control chromosomes in the GnomAD database, including 2,674 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 0.094 ( 745 hom., cov: 31)

Exomes 𝑓: 0.090 ( 1929 hom. )

Consequence

RBM17
NM_032905.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.629

Publications

6 publications found

Variant links:

Genes affected

RBM17 (HGNC:16944): (RNA binding motif protein 17) This gene encodes an RNA binding protein. The encoded protein is part of the spliceosome complex and functions in the second catalytic step of mRNA splicing. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 9 and 15. [provided by RefSeq, Mar 2009]

RBM17 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM17	NM_032905.5 link	c.506-148A>C		intron_variant	Intron 5 of 11	ENST00000379888.9	NP_116294.1	Q96I25Q5W009
RBM17	NM_001145547.2 link	c.506-148A>C		intron_variant	Intron 5 of 11		NP_001139019.1	Q96I25Q5W009

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM17	ENST00000379888.9 link	c.506-148A>C		intron_variant	Intron 5 of 11	1	NM_032905.5	ENSP00000369218.4		Q96I25

Frequencies

GnomAD3 genomes

AF:

0.0944

AC:

14336

AN:

151924

Hom.:

744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0828

Gnomad ASJ

AF:

0.0666

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0910

Gnomad FIN

AF:

0.0824

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0953

GnomAD4 exome

AF:

0.0900

AC:

36278

AN:

403086

Hom.:

1929

Cov.:

AF XY:

0.0895

AC XY:

19031

AN XY:

212592

show subpopulations

African (AFR)

AF:

0.120

AC:

1162

AN:

9674

American (AMR)

AF:

0.0588

AC:

691

AN:

11748

Ashkenazi Jewish (ASJ)

AF:

0.0690

AC:

846

AN:

12258

East Asian (EAS)

AF:

0.190

AC:

4997

AN:

26300

South Asian (SAS)

AF:

0.0871

AC:

3004

AN:

34502

European-Finnish (FIN)

AF:

0.0848

AC:

3716

AN:

43836

Middle Eastern (MID)

AF:

0.120

AC:

213

AN:

1770

European-Non Finnish (NFE)

AF:

0.0806

AC:

19341

AN:

239866

Other (OTH)

AF:

0.0998

AC:

2308

AN:

23132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1574

3148

4722

6296

7870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0944

AC:

14354

AN:

152042

Hom.:

745

Cov.:

AF XY:

0.0953

AC XY:

7085

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.119

AC:

4922

AN:

41446

American (AMR)

AF:

0.0827

AC:

1263

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

231

AN:

3468

East Asian (EAS)

AF:

0.187

AC:

969

AN:

5184

South Asian (SAS)

AF:

0.0915

AC:

441

AN:

4818

European-Finnish (FIN)

AF:

0.0824

AC:

871

AN:

10564

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0796

AC:

5410

AN:

67974

Other (OTH)

AF:

0.0972

AC:

205

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

654

1308

1962

2616

3270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0788

Hom.:

642

Bravo

AF:

0.0948

Asia WGS

AF:

0.136

AC:

473

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

(source)

DANN

Benign

0.71

PhyloP100

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over