Variant chr7-128313190-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_018077.3(RBM28):c.2130A>G(p.Gln710=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 1,613,736 control chromosomes in the GnomAD database, including 6,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1521 hom., cov: 32)

Exomes 𝑓: 0.072 ( 4711 hom. )

Consequence

RBM28
NM_018077.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.709

Variant links:

Genes affected

RBM28 (HGNC:21863): (RNA binding motif protein 28) The protein encoded by this gene is a specific nucleolar component of the spliceosomal small nuclear ribonucleoprotein (snRNP)complexes . It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), possibly coordinating their transition through the nucleolus. Mutation in this gene causes alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome), a pleiotropic and clinically heterogeneous disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

RBM28 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-128313190-T-C is Benign according to our data. Variant chr7-128313190-T-C is described in ClinVar as [Benign]. Clinvar id is 3055490.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.709 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM28	NM_018077.3 linkuse as main transcript	c.2130A>G	p.Gln710=	synonymous_variant	18/19	ENST00000223073.6
RBM28	NM_001166135.2 linkuse as main transcript	c.1707A>G	p.Gln569=	synonymous_variant	14/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM28	ENST00000223073.6 linkuse as main transcript	c.2130A>G	p.Gln710=	synonymous_variant	18/19	1	NM_018077.3	P1	Q9NW13-1
RBM28	ENST00000415472.6 linkuse as main transcript	c.1707A>G	p.Gln569=	synonymous_variant	14/15	2			Q9NW13-2
RBM28	ENST00000481788.1 linkuse as main transcript	n.502A>G		non_coding_transcript_exon_variant	3/4	3
RBM28	ENST00000495327.1 linkuse as main transcript	n.293A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16955

AN:

152066

Hom.:

1511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0553

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0543

Gnomad FIN

AF:

0.0418

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0714

Gnomad OTH

AF:

0.0907

GnomAD3 exomes

AF:

0.0654

AC:

16460

AN:

251492

Hom.:

938

AF XY:

0.0621

AC XY:

8443

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.0376

Gnomad ASJ exome

AF:

0.0508

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0473

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0688

Gnomad OTH exome

AF:

0.0704

GnomAD4 exome

AF:

0.0715

AC:

104515

AN:

1461552

Hom.:

4711

Cov.:

AF XY:

0.0701

AC XY:

50972

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.0395

Gnomad4 ASJ exome

AF:

0.0492

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0482

Gnomad4 FIN exome

AF:

0.0464

Gnomad4 NFE exome

AF:

0.0732

Gnomad4 OTH exome

AF:

0.0765

GnomAD4 genome

AF:

0.112

AC:

16997

AN:

152184

Hom.:

1521

Cov.:

AF XY:

0.107

AC XY:

7999

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.0552

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0546

Gnomad4 FIN

AF:

0.0418

Gnomad4 NFE

AF:

0.0714

Gnomad4 OTH

AF:

0.0903

Alfa

AF:

0.0770

Hom.:

1093

Bravo

AF:

0.120

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

EpiCase

AF:

0.0696

EpiControl

AF:

0.0727

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RBM28-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.84

DANN

Benign

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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