dbSNP rs2023953: RBM6:p.Gln975Gln (chr3-50066484-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_005777.3(RBM6):c.2925G>A(p.Gln975Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,370 control chromosomes in the GnomAD database, including 8,518 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 ( 744 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7774 hom. )

Consequence

RBM6
NM_005777.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

Publications

21 publications found

Variant links:

Genes affected

RBM6 (HGNC:9903): (RNA binding motif protein 6) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RBM6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP7

Synonymous conserved (PhyloP=1.85 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM6	NM_005777.3 link	c.2925G>A	p.Gln975Gln	synonymous_variant	Exon 17 of 21	ENST00000266022.9	NP_005768.1	P78332-1A8K6Q4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM6	ENST00000266022.9 link	c.2925G>A	p.Gln975Gln	synonymous_variant	Exon 17 of 21	1	NM_005777.3	ENSP00000266022.4		P78332-1

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14266

AN:

152166

Hom.:

741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0770

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.0569

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.0946

GnomAD2 exomes

AF:

0.0974

AC:

24022

AN:

246580

AF XY:

0.0941

show subpopulations

Gnomad AFR exome

AF:

0.0751

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.0505

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.101

AC:

148052

AN:

1461086

Hom.:

7774

Cov.:

AF XY:

0.0994

AC XY:

72235

AN XY:

726812

show subpopulations

African (AFR)

AF:

0.0744

AC:

2491

AN:

33472

American (AMR)

AF:

0.127

AC:

5698

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

3909

AN:

26136

East Asian (EAS)

AF:

0.0589

AC:

2338

AN:

39700

South Asian (SAS)

AF:

0.0530

AC:

4569

AN:

86256

European-Finnish (FIN)

AF:

0.0989

AC:

5217

AN:

52754

Middle Eastern (MID)

AF:

0.0756

AC:

436

AN:

5768

European-Non Finnish (NFE)

AF:

0.106

AC:

117534

AN:

1111896

Other (OTH)

AF:

0.0971

AC:

5860

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

7504

15008

22511

30015

37519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4294

8588

12882

17176

21470

<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:

0.0938

AC:

14284

AN:

152284

Hom.:

744

Cov.:

AF XY:

0.0930

AC XY:

6921

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0768

AC:

3193

AN:

41556

American (AMR)

AF:

0.104

AC:

1594

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

545

AN:

3470

East Asian (EAS)

AF:

0.0511

AC:

265

AN:

5184

South Asian (SAS)

AF:

0.0572

AC:

276

AN:

4828

European-Finnish (FIN)

AF:

0.103

AC:

1087

AN:

10604

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7021

AN:

68030

Other (OTH)

AF:

0.0936

AC:

198

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

663

1327

1990

2654

3317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<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:

0.102

Hom.:

1703

Bravo

AF:

0.0950

Asia WGS

AF:

0.0640

AC:

223

AN:

3478

EpiCase

AF:

0.109

EpiControl

AF:

0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.6

(source)

DANN

Benign

0.68

PhyloP100

1.9

PromoterAI

-0.0072

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=251/49

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