Genetic Variant RBM3:c.-13-57C>G (chrX-48575111-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006743.5(RBM3):c.-13-57C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 110,678 control chromosomes in the GnomAD database, including 9,715 homozygotes. There are 15,848 hemizygotes in GnomAD. 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 0.47 ( 9715 hom., 15848 hem., cov: 23)

Exomes 𝑓: 0.57 ( 90624 hom. 125167 hem. )

Failed GnomAD Quality Control

Consequence

RBM3
NM_006743.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

8 publications found

Variant links:

Genes affected

RBM3 (HGNC:9900): (RNA binding motif protein 3) This gene is a member of the glycine-rich RNA-binding protein family and encodes a protein with one RNA recognition motif (RRM) domain. Expression of this gene is induced by cold shock and low oxygen tension. A pseudogene exists on chromosome 1. Multiple alternatively spliced transcript variants that are predicted to encode different isoforms have been characterized although some of these variants fit nonsense-mediated decay (NMD) criteria. [provided by RefSeq, Jul 2008]

RBM3 links:

ENSG00000204620 (HGNC:):

ENSG00000204620 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM3	NM_006743.5 link	c.-13-57C>G		intron_variant	Intron 1 of 6	ENST00000376759.8	NP_006734.1	P98179A0A024QYX3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM3	ENST00000376759.8 link	c.-13-57C>G		intron_variant	Intron 1 of 6	1	NM_006743.5	ENSP00000365950.3		P98179

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

52555

AN:

110627

Hom.:

9731

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.676

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.494

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.572

AC:

439090

AN:

767708

Hom.:

90624

Cov.:

AF XY:

0.584

AC XY:

125167

AN XY:

214212

show subpopulations

African (AFR)

AF:

0.228

AC:

4399

AN:

19321

American (AMR)

AF:

0.579

AC:

16074

AN:

27774

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

11591

AN:

16817

East Asian (EAS)

AF:

0.472

AC:

12541

AN:

26583

South Asian (SAS)

AF:

0.571

AC:

25071

AN:

43943

European-Finnish (FIN)

AF:

0.580

AC:

21447

AN:

36959

Middle Eastern (MID)

AF:

0.606

AC:

2122

AN:

3504

European-Non Finnish (NFE)

AF:

0.585

AC:

326058

AN:

557645

Other (OTH)

AF:

0.563

AC:

19787

AN:

35162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6902

13804

20706

27608

34510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8510

17020

25530

34040

42550

<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:

0.475

AC:

52542

AN:

110678

Hom.:

9715

Cov.:

AF XY:

0.481

AC XY:

15848

AN XY:

32926

show subpopulations

African (AFR)

AF:

0.231

AC:

7049

AN:

30552

American (AMR)

AF:

0.544

AC:

5635

AN:

10352

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

1779

AN:

2630

East Asian (EAS)

AF:

0.473

AC:

1644

AN:

3478

South Asian (SAS)

AF:

0.545

AC:

1440

AN:

2643

European-Finnish (FIN)

AF:

0.573

AC:

3338

AN:

5829

Middle Eastern (MID)

AF:

0.587

AC:

125

AN:

213

European-Non Finnish (NFE)

AF:

0.574

AC:

30322

AN:

52820

Other (OTH)

AF:

0.495

AC:

740

AN:

1494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

909

1818

2727

3636

4545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.508

Hom.:

3654

Bravo

AF:

0.465

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.54

(source)

DANN

Benign

0.52

PhyloP100

-1.9

PromoterAI

0.086

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.95

Mutation Taster

=300/0

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