Genetic Variant NM_001003793.3:c.745-135A>G (chr3-29884027-A-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_001003793.3(RBMS3):c.745-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 698,810 control chromosomes in the GnomAD database, including 44,214 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 0.39 ( 12000 hom., cov: 32)

Exomes 𝑓: 0.34 ( 32214 hom. )

Consequence

RBMS3
NM_001003793.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

3 publications found

Variant links:

Genes affected

RBMS3 (HGNC:13427): (RNA binding motif single stranded interacting protein 3) This gene encodes an RNA-binding protein that belongs to the c-myc gene single-strand binding protein family. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. The encoded protein was isolated by virtue of its binding to an upstream element of the alpha2(I) collagen promoter. The observation that this protein localizes mostly in the cytoplasm suggests that it may be involved in a cytoplasmic function such as controlling RNA metabolism, rather than transcription. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

RBMS3 links:

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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 = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS3	NM_001003793.3 link	c.745-135A>G		intron_variant	Intron 7 of 14	ENST00000383767.7	NP_001003793.1	Q6XE24-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7 link	c.745-135A>G		intron_variant	Intron 7 of 14	1	NM_001003793.3	ENSP00000373277.2		Q6XE24-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58715

AN:

151688

Hom.:

11972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.287

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.353

GnomAD4 exome

AF:

0.337

AC:

184500

AN:

547004

Hom.:

32214

AF XY:

0.335

AC XY:

95913

AN XY:

286206

show subpopulations

African (AFR)

AF:

0.514

AC:

7129

AN:

13880

American (AMR)

AF:

0.375

AC:

7052

AN:

18806

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

4105

AN:

14042

East Asian (EAS)

AF:

0.182

AC:

5666

AN:

31164

South Asian (SAS)

AF:

0.320

AC:

14095

AN:

44082

European-Finnish (FIN)

AF:

0.389

AC:

15352

AN:

39416

Middle Eastern (MID)

AF:

0.271

AC:

994

AN:

3672

European-Non Finnish (NFE)

AF:

0.341

AC:

120499

AN:

353580

Other (OTH)

AF:

0.339

AC:

9608

AN:

28362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5729

11458

17188

22917

28646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1886

3772

5658

7544

9430

<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:

0.387

AC:

58792

AN:

151806

Hom.:

12000

Cov.:

AF XY:

0.385

AC XY:

28556

AN XY:

74198

show subpopulations

African (AFR)

AF:

0.513

AC:

21236

AN:

41414

American (AMR)

AF:

0.359

AC:

5467

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

991

AN:

3454

East Asian (EAS)

AF:

0.176

AC:

907

AN:

5140

South Asian (SAS)

AF:

0.330

AC:

1588

AN:

4808

European-Finnish (FIN)

AF:

0.385

AC:

4065

AN:

10564

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23289

AN:

67878

Other (OTH)

AF:

0.350

AC:

739

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1804

3608

5412

7216

9020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.351

Hom.:

40168

Bravo

AF:

0.393

Asia WGS

AF:

0.276

AC:

962

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

0.58

(source)

DANN

Benign

0.34

PhyloP100

-1.2

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