Genetic Variant RBBP6:c.1590-6T>C (chr16-24567137-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_006910.5(RBBP6):c.1590-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,604,408 control chromosomes in the GnomAD database, including 237,587 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 30175 hom., cov: 31)

Exomes 𝑓: 0.53 ( 207412 hom. )

Consequence

RBBP6
NM_006910.5 splice_region, intron

Scores

Splicing: ADA: 0.00002483

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.786

Variant links:

Genes affected

RBBP6 (HGNC:9889): (RB binding protein 6, ubiquitin ligase) The retinoblastoma tumor suppressor (pRB) protein binds with many other proteins. In various human cancers, pRB suppresses cellular proliferation and is inactivated. Cell cycle-dependent phosphorylation regulates the activity of pRB. This gene encodes a protein which binds to underphosphorylated but not phosphorylated pRB. Multiple alternatively spliced transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RBBP6 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=-0.55).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBBP6	NM_006910.5 link	c.1590-6T>C		splice_region_variant, intron_variant	Intron 14 of 17	ENST00000319715.10	NP_008841.2
RBBP6	NM_018703.4 link	c.1590-6T>C		splice_region_variant, intron_variant	Intron 14 of 16		NP_061173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBBP6	ENST00000319715.10 link	c.1590-6T>C		splice_region_variant, intron_variant	Intron 14 of 17	1	NM_006910.5	ENSP00000317872.4		Q7Z6E9-1

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92911

AN:

151964

Hom.:

30126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.608

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.505

Gnomad OTH

AF:

0.605

GnomAD2 exomes

AF:

0.559

AC:

137964

AN:

246708

AF XY:

0.560

show subpopulations

Gnomad AFR exome

AF:

0.843

Gnomad AMR exome

AF:

0.581

Gnomad ASJ exome

AF:

0.550

Gnomad EAS exome

AF:

0.401

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.509

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.529

AC:

768351

AN:

1452324

Hom.:

207412

Cov.:

AF XY:

0.533

AC XY:

383945

AN XY:

721012

show subpopulations

Gnomad4 AFR exome

AF:

0.849

AC:

28236

AN:

33260

Gnomad4 AMR exome

AF:

0.583

AC:

25947

AN:

44472

Gnomad4 ASJ exome

AF:

0.543

AC:

14073

AN:

25908

Gnomad4 EAS exome

AF:

0.407

AC:

16083

AN:

39468

Gnomad4 SAS exome

AF:

0.695

AC:

59848

AN:

86062

Gnomad4 FIN exome

AF:

0.509

AC:

27070

AN:

53226

Gnomad4 NFE exome

AF:

0.508

AC:

560759

AN:

1104230

Gnomad4 Remaining exome

AF:

0.550

AC:

33010

AN:

59966

Heterozygous variant carriers

18739

37478

56216

74955

93694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

16482

32964

49446

65928

82410

<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:

0.612

AC:

93010

AN:

152084

Hom.:

30175

Cov.:

AF XY:

0.613

AC XY:

45535

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.836

AC:

0.836434

AN:

0.836434

Gnomad4 AMR

AF:

0.608

AC:

0.607512

AN:

0.607512

Gnomad4 ASJ

AF:

0.554

AC:

0.55389

AN:

0.55389

Gnomad4 EAS

AF:

0.413

AC:

0.412858

AN:

0.412858

Gnomad4 SAS

AF:

0.702

AC:

0.702159

AN:

0.702159

Gnomad4 FIN

AF:

0.512

AC:

0.511646

AN:

0.511646

Gnomad4 NFE

AF:

0.505

AC:

0.505164

AN:

0.505164

Gnomad4 OTH

AF:

0.606

AC:

0.60596

AN:

0.60596

Heterozygous variant carriers

1669

3339

5008

6678

8347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.544

Hom.:

74673

Bravo

AF:

0.625

Asia WGS

AF:

0.596

AC:

2072

AN:

3478

EpiCase

AF:

0.506

EpiControl

AF:

0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.68

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000025

dbscSNV1_RF

Benign

0.0040

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over