Genetic Variant NM_018989.2:c.526C>G (chr5-146229847-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018989.2(RBM27):c.526C>G(p.Leu176Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RBM27
NM_018989.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610

Publications

0 publications found

Variant links:

Genes affected

RBM27 (HGNC:29243): (RNA binding motif protein 27) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be located in cytoplasm and nuclear speck. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RBM27 links:

ENSG00000275740 (HGNC:58349):

ENSG00000275740 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07760355).

BS2

High AC in GnomAdExome4 at 45 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018989.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM27	NM_018989.2	MANE Select	c.526C>G	p.Leu176Val	missense	Exon 5 of 21	NP_061862.1	Q9P2N5
	RBM27-POU4F3	NM_001414499.1		c.526C>G	p.Leu176Val	missense	Exon 5 of 20	NP_001401428.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBM27	ENST00000265271.7	TSL:1 MANE Select	c.526C>G	p.Leu176Val	missense	Exon 5 of 21	ENSP00000265271.5	Q9P2N5
ENSG00000275740	ENST00000506502.2	TSL:5	c.526C>G	p.Leu176Val	missense	Exon 5 of 20	ENSP00000475384.1	U3KPZ7
RBM27	ENST00000861565.1		c.526C>G	p.Leu176Val	missense	Exon 5 of 21	ENSP00000531624.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000284

AC:

AN:

246590

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000453

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461750

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1111948

Other (OTH)

AF:

0.0000828

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000249

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.80

M_CAP

Benign

0.0067

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

-0.061

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.85

REVEL

Benign

0.044

Sift

Benign

0.24

Sift4G

Benign

0.50

Polyphen

0.79

Vest4

0.22

MutPred

0.20

Gain of methylation at K172 (P = 0.1006)

MVP

0.20

MPC

0.34

ClinPred

0.043

GERP RS

2.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.043

gMVP

0.24

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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