7-128314794-G-A

Position:

chr7-128314794-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_018077.3(RBM28):c.2015C>T(p.Ala672Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,142 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00071 ( 9 hom. )

Consequence

RBM28
NM_018077.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.459

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031175315).

BP6

Variant 7-128314794-G-A is Benign according to our data. Variant chr7-128314794-G-A is described in ClinVar as [Benign]. Clinvar id is 787865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00593 (903/152254) while in subpopulation AFR AF= 0.0202 (840/41550). AF 95% confidence interval is 0.0191. There are 10 homozygotes in gnomad4. There are 412 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM28	NM_018077.3 linkuse as main transcript	c.2015C>T	p.Ala672Val	missense_variant	17/19	ENST00000223073.6
RBM28	NM_001166135.2 linkuse as main transcript	c.1592C>T	p.Ala531Val	missense_variant	13/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM28	ENST00000223073.6 linkuse as main transcript	c.2015C>T	p.Ala672Val	missense_variant	17/19	1	NM_018077.3	P1	Q9NW13-1
RBM28	ENST00000415472.6 linkuse as main transcript	c.1592C>T	p.Ala531Val	missense_variant	13/15	2			Q9NW13-2
RBM28	ENST00000481788.1 linkuse as main transcript	n.387C>T		non_coding_transcript_exon_variant	2/4	3
RBM28	ENST00000495327.1 linkuse as main transcript	n.178C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00593

AC:

902

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00156

AC:

391

AN:

250162

Hom.:

AF XY:

0.00112

AC XY:

151

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.0200

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000714

AC:

1044

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000630

AC XY:

458

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000200

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.00593

AC:

903

AN:

152254

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

412

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0202

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00640

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0177

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00186

AC:

226

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.4

DANN

Benign

0.78

DEOGEN2

Benign

0.0097

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.58

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.12

Sift

Benign

0.41

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0040

B;.

Vest4

0.084

MVP

0.092

MPC

0.14

ClinPred

0.0042

GERP RS

-1.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.017

gMVP

0.083

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