Genetic Variant NM_001077351.2:c.-129T>G (chr14-22919117-A-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_001077351.2(RBM23):c.-129T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,052 control chromosomes in the GnomAD database, including 25,342 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 0.57 ( 25318 hom., cov: 31)

Exomes 𝑓: 0.68 ( 24 hom. )

Consequence

RBM23
NM_001077351.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.344

Publications

20 publications found

Variant links:

Genes affected

RBM23 (HGNC:20155): (RNA binding motif protein 23) This gene encodes a member of the U2AF-like family of RNA binding proteins. This protein interacts with some steroid nuclear receptors, localizes to the promoter of a steroid- responsive gene, and increases transcription of steroid-responsive transcriptional reporters in a hormone-dependent manner. It is also implicated in the steroid receptor-dependent regulation of alternative splicing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RBM23 links:

PRMT5-AS1 (HGNC:40533): (PRMT5 antisense RNA 1)

PRMT5-AS1 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077351.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBM23	NM_001077351.2	MANE Select	c.-129T>G	5_prime_UTR	Exon 1 of 14	NP_001070819.1	Q86U06-1
RBM23	NM_001352764.2		c.-119T>G	5_prime_UTR	Exon 1 of 15	NP_001339693.1
RBM23	NM_001352763.2		c.-247T>G	5_prime_UTR	Exon 1 of 15	NP_001339692.1	A0A0S2Z5D9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBM23	ENST00000359890.8	TSL:1 MANE Select	c.-129T>G	5_prime_UTR	Exon 1 of 14	ENSP00000352956.3	Q86U06-1
RBM23	ENST00000399922.6	TSL:1	c.-129T>G	5_prime_UTR	Exon 1 of 13	ENSP00000382806.2	Q86U06-2
RBM23	ENST00000555209.5	TSL:1	c.-611T>G	5_prime_UTR	Exon 1 of 11	ENSP00000452602.1	G3V5Z6

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86062

AN:

151844

Hom.:

25296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.791

Gnomad SAS

AF:

0.752

Gnomad FIN

AF:

0.591

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.613

Gnomad OTH

AF:

0.590

GnomAD4 exome

AF:

0.682

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.671

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.567

AC:

86124

AN:

151964

Hom.:

25318

Cov.:

AF XY:

0.570

AC XY:

42361

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.418

AC:

17321

AN:

41452

American (AMR)

AF:

0.597

AC:

9119

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1987

AN:

3470

East Asian (EAS)

AF:

0.792

AC:

4083

AN:

5158

South Asian (SAS)

AF:

0.754

AC:

3635

AN:

4822

European-Finnish (FIN)

AF:

0.591

AC:

6230

AN:

10534

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.613

AC:

41661

AN:

67954

Other (OTH)

AF:

0.587

AC:

1233

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1844

3688

5532

7376

9220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

746

1492

2238

2984

3730

<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:

0.600

Hom.:

35061

Bravo

AF:

0.561

Asia WGS

AF:

0.736

AC:

2559

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.3

(source)

DANN

Benign

0.45

PhyloP100

0.34

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over