Genetic Variant RBM5:p.Tyr679Tyr (chr3-50115923-T-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_005778.4(RBM5):c.2037T>C(p.Tyr679Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,612,388 control chromosomes in the GnomAD database, including 307,161 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 0.65 ( 33139 hom., cov: 32)

Exomes 𝑓: 0.61 ( 274022 hom. )

Consequence

RBM5
NM_005778.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

43 publications found

Variant links:

Genes affected

RBM5 (HGNC:9902): (RNA binding motif protein 5) This gene is a candidate tumor suppressor gene which encodes a nuclear RNA binding protein that is a component of the spliceosome A complex. The encoded protein plays a role in the induction of cell cycle arrest and apoptosis through pre-mRNA splicing of multiple target genes including the tumor suppressor protein p53. This gene is located within the tumor suppressor region 3p21.3, and may play a role in the inhibition of tumor transformation and progression of several malignancies including lung cancer. [provided by RefSeq, Oct 2011]

RBM5 links:

SEMA3F-AS1 (HGNC:40518): (SEMA3F antisense RNA 1)

SEMA3F-AS1 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=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM5	NM_005778.4 link	c.2037T>C	p.Tyr679Tyr	synonymous_variant	Exon 22 of 25	ENST00000347869.8	NP_005769.1	P52756-1A0A024R2U6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM5	ENST00000347869.8 link	c.2037T>C	p.Tyr679Tyr	synonymous_variant	Exon 22 of 25	1	NM_005778.4	ENSP00000343054.3		P52756-1

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99339

AN:

151984

Hom.:

33093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.741

Gnomad EAS

AF:

0.885

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.575

Gnomad OTH

AF:

0.640

GnomAD2 exomes

AF:

0.675

AC:

169668

AN:

251410

AF XY:

0.673

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.761

Gnomad ASJ exome

AF:

0.735

Gnomad EAS exome

AF:

0.884

Gnomad FIN exome

AF:

0.621

Gnomad NFE exome

AF:

0.573

Gnomad OTH exome

AF:

0.636

GnomAD4 exome

AF:

0.606

AC:

884777

AN:

1460286

Hom.:

274022

Cov.:

AF XY:

0.611

AC XY:

443722

AN XY:

726532

show subpopulations

African (AFR)

AF:

0.733

AC:

24529

AN:

33442

American (AMR)

AF:

0.752

AC:

33616

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.733

AC:

19156

AN:

26134

East Asian (EAS)

AF:

0.871

AC:

34552

AN:

39684

South Asian (SAS)

AF:

0.822

AC:

70914

AN:

86224

European-Finnish (FIN)

AF:

0.617

AC:

32960

AN:

53404

Middle Eastern (MID)

AF:

0.651

AC:

3755

AN:

5768

European-Non Finnish (NFE)

AF:

0.565

AC:

627656

AN:

1110574

Other (OTH)

AF:

0.624

AC:

37639

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16409

32818

49227

65636

82045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17718

35436

53154

70872

88590

<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:

0.654

AC:

99438

AN:

152102

Hom.:

33139

Cov.:

AF XY:

0.662

AC XY:

49198

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.729

AC:

30244

AN:

41494

American (AMR)

AF:

0.679

AC:

10374

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.741

AC:

2572

AN:

3472

East Asian (EAS)

AF:

0.886

AC:

4582

AN:

5172

South Asian (SAS)

AF:

0.829

AC:

3994

AN:

4816

European-Finnish (FIN)

AF:

0.618

AC:

6530

AN:

10558

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.575

AC:

39103

AN:

67996

Other (OTH)

AF:

0.637

AC:

1343

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1746

3492

5238

6984

8730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.607

Hom.:

62836

Bravo

AF:

0.655

Asia WGS

AF:

0.799

AC:

2778

AN:

3478

EpiCase

AF:

0.581

EpiControl

AF:

0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.6

(source)

DANN

Benign

0.80

PhyloP100

0.030

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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