Genetic Variant NM_018191.4:c.643C>T (chr13-49552246-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_018191.4(RCBTB1):c.643C>T(p.Leu215Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,601,994 control chromosomes in the GnomAD database, including 573,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55192 hom., cov: 30)

Exomes 𝑓: 0.84 ( 518292 hom. )

Consequence

RCBTB1
NM_018191.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.881

Variant links:

Genes affected

RCBTB1 (HGNC:18243): (RCC1 and BTB domain containing protein 1) This gene encodes a protein with an N-terminal RCC1 domain and a C-terminal BTB (broad complex, tramtrack and bric-a-brac) domain. In rat, over-expression of this gene in vascular smooth muscle cells induced cellular hypertrophy. In rat, the C-terminus of RCBTB1 interacts with the angiotensin II receptor-1A. In humans, this gene maps to a region of chromosome 13q that is frequently deleted in B-cell chronic lymphocytic leukemia and other lymphoid malignancies. [provided by RefSeq, Jul 2008]

RCBTB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 13-49552246-G-A is Benign according to our data. Variant chr13-49552246-G-A is described in ClinVar as [Benign]. Clinvar id is 1170496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.881 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCBTB1	NM_018191.4 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 7 of 13	ENST00000378302.7	NP_060661.3	Q8NDN9-1B3KR20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RCBTB1	ENST00000378302.7 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 7 of 13	1	NM_018191.4	ENSP00000367552.2	Q8NDN9-1
RCBTB1	ENST00000258646.3 link	c.643C>T	p.Leu215Leu	synonymous_variant	Exon 5 of 11	2		ENSP00000258646.3	Q8NDN9-1
RCBTB1	ENST00000490058.1 link	n.7C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.851

AC:

129286

AN:

151976

Hom.:

55125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.888

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.865

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.895

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.798

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.837

Gnomad OTH

AF:

0.832

GnomAD3 exomes

AF:

0.847

AC:

197908

AN:

233604

Hom.:

83962

AF XY:

0.842

AC XY:

105938

AN XY:

125776

show subpopulations

Gnomad AFR exome

AF:

0.893

Gnomad AMR exome

AF:

0.904

Gnomad ASJ exome

AF:

0.815

Gnomad EAS exome

AF:

0.893

Gnomad SAS exome

AF:

0.816

Gnomad FIN exome

AF:

0.808

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.845

AC:

1225152

AN:

1449900

Hom.:

518292

Cov.:

AF XY:

0.843

AC XY:

607215

AN XY:

720072

show subpopulations

Gnomad4 AFR exome

AF:

0.884

Gnomad4 AMR exome

AF:

0.899

Gnomad4 ASJ exome

AF:

0.817

Gnomad4 EAS exome

AF:

0.884

Gnomad4 SAS exome

AF:

0.815

Gnomad4 FIN exome

AF:

0.811

Gnomad4 NFE exome

AF:

0.845

Gnomad4 OTH exome

AF:

0.847

GnomAD4 genome

AF:

0.851

AC:

129413

AN:

152094

Hom.:

55192

Cov.:

AF XY:

0.848

AC XY:

63060

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.888

Gnomad4 AMR

AF:

0.865

Gnomad4 ASJ

AF:

0.796

Gnomad4 EAS

AF:

0.895

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.798

Gnomad4 NFE

AF:

0.837

Gnomad4 OTH

AF:

0.833

Alfa

AF:

0.846

Hom.:

27883

Bravo

AF:

0.858

Asia WGS

AF:

0.862

AC:

2998

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RCBTB1-related retinopathy

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.7

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over