dbSNP rs2075387: RBM19:p.Arg921Gln (chr12-113844691-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016196.4(RBM19):c.2762G>A(p.Arg921Gln) variant causes a missense change. The variant allele was found at a frequency of 0.261 in 1,609,256 control chromosomes in the GnomAD database, including 56,295 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 0.24 ( 4788 hom., cov: 33)

Exomes 𝑓: 0.26 ( 51507 hom. )

Consequence

RBM19
NM_016196.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.72

Publications

24 publications found

Variant links:

Genes affected

RBM19 (HGNC:29098): (RNA binding motif protein 19) This gene encodes a nucleolar protein that contains six RNA-binding motifs. The encoded protein may be involved in regulating ribosome biogenesis. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Apr 2009]

RBM19 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 (MetaRNN=0.0017284453).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM19	NM_016196.4 link	c.2762G>A	p.Arg921Gln	missense_variant	Exon 23 of 24	ENST00000261741.10	NP_057280.2	Q9Y4C8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RBM19	ENST00000261741.10 link	c.2762G>A	p.Arg921Gln	missense_variant	Exon 23 of 24	1	NM_016196.4	ENSP00000261741.5	Q9Y4C8
RBM19	ENST00000392561.7 link	c.2762G>A	p.Arg921Gln	missense_variant	Exon 23 of 25	1		ENSP00000376344.3	Q9Y4C8
RBM19	ENST00000545145.6 link	c.2762G>A	p.Arg921Gln	missense_variant	Exon 23 of 25	2		ENSP00000442053.2	Q9Y4C8
RBM19	ENST00000552384.1 link	n.212G>A		non_coding_transcript_exon_variant	Exon 2 of 4	3		ENSP00000449604.1	H0YIL2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37231

AN:

152096

Hom.:

4782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.245

AC:

59587

AN:

242782

AF XY:

0.252

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.294

Gnomad EAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.266

Gnomad OTH exome

AF:

0.267

GnomAD4 exome

AF:

0.263

AC:

383432

AN:

1457042

Hom.:

51507

Cov.:

AF XY:

0.265

AC XY:

192028

AN XY:

724590

show subpopulations

African (AFR)

AF:

0.183

AC:

6100

AN:

33398

American (AMR)

AF:

0.182

AC:

8082

AN:

44318

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7480

AN:

26054

East Asian (EAS)

AF:

0.158

AC:

6263

AN:

39572

South Asian (SAS)

AF:

0.293

AC:

25112

AN:

85644

European-Finnish (FIN)

AF:

0.329

AC:

17121

AN:

52100

Middle Eastern (MID)

AF:

0.332

AC:

1906

AN:

5738

European-Non Finnish (NFE)

AF:

0.267

AC:

295941

AN:

1110026

Other (OTH)

AF:

0.256

AC:

15427

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

16016

32032

48047

64063

80079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9770

19540

29310

39080

48850

<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:

0.245

AC:

37256

AN:

152214

Hom.:

4788

Cov.:

AF XY:

0.248

AC XY:

18436

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.181

AC:

7506

AN:

41562

American (AMR)

AF:

0.207

AC:

3165

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

998

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

737

AN:

5164

South Asian (SAS)

AF:

0.299

AC:

1444

AN:

4828

European-Finnish (FIN)

AF:

0.343

AC:

3638

AN:

10594

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.277

AC:

18829

AN:

67986

Other (OTH)

AF:

0.259

AC:

548

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1424

2847

4271

5694

7118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.259

Hom.:

17443

Bravo

AF:

0.230

TwinsUK

AF:

0.264

AC:

978

ALSPAC

AF:

0.257

AC:

991

ESP6500AA

AF:

0.176

AC:

776

ESP6500EA

AF:

0.270

AC:

2321

ExAC

AF:

0.248

AC:

30086

Asia WGS

AF:

0.208

AC:

728

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.96

.;.;D

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.0

M;M;M

PhyloP100

4.7

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.011

D;D;D

Sift4G

Uncertain

0.030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.26

MPC

0.20

ClinPred

0.020

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.55

Mutation Taster

=93/7

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