Genetic Variant RBM28:c.1788+110T>C (chr7-128317549-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018077.3(RBM28):c.1788+110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,914 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RBM28
NM_018077.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

ANE syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

RBM28 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM28	NM_018077.3 link	c.1788+110T>C		intron_variant	Intron 16 of 18	ENST00000223073.6	NP_060547.2
RBM28	NM_001166135.2 link	c.1365+110T>C		intron_variant	Intron 12 of 14		NP_001159607.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
RBM28	ENST00000223073.6 link	c.1788+110T>C	intron_variant	Intron 16 of 18	1	NM_018077.3	ENSP00000223073.1
RBM28	ENST00000415472.6 link	c.1365+110T>C	intron_variant	Intron 12 of 14	2		ENSP00000390517.2
RBM28	ENST00000481788.1 link	n.161-2529T>C	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

678230

Hom.:

AF XY:

0.00

AC XY:

AN XY:

362936

African (AFR)

AF:

0.00

AC:

AN:

18126

American (AMR)

AF:

0.00

AC:

AN:

36822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20546

East Asian (EAS)

AF:

0.00

AC:

AN:

34940

South Asian (SAS)

AF:

0.00

AC:

AN:

66110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2880

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

424068

Other (OTH)

AF:

0.00

AC:

AN:

34224

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.8

(source)

DANN

Benign

0.63

PhyloP100

1.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over