Variant 10-42791700-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBA1

The NM_014753.4(BMS1):c.710G>A(p.Arg237His) variant causes a missense change. The variant allele was found at a frequency of 0.00367 in 1,613,602 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0050 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 110 hom. )

Consequence

BMS1
NM_014753.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.73

Variant links:

Genes affected

BMS1 (HGNC:23505): (BMS1 ribosome biogenesis factor) This gene likely encodes a ribosome assembly protein. A similar protein in yeast functions in 35S-rRNA processing, which includes a series of cleavage steps critical for formation of 40S ribosomes. Related pseudogenes exist on chromosomes 2, 9, 10, 15, 16, and 22.[provided by RefSeq, Mar 2009]

BMS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, PROVEAN [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.010611266).

BP6

Variant 10-42791700-G-A is Benign according to our data. Variant chr10-42791700-G-A is described in ClinVar as [Benign]. Clinvar id is 782289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMS1	NM_014753.4 linkuse as main transcript	c.710G>A	p.Arg237His	missense_variant	6/23	ENST00000374518.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMS1	ENST00000374518.6 linkuse as main transcript	c.710G>A	p.Arg237His	missense_variant	6/23	1	NM_014753.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00499

AC:

759

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0560

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00652

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0113

AC:

2841

AN:

250886

Hom.:

AF XY:

0.00966

AC XY:

1310

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.0419

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.0572

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.00721

Gnomad NFE exome

AF:

0.000494

Gnomad OTH exome

AF:

0.00735

GnomAD4 exome

AF:

0.00354

AC:

5170

AN:

1461350

Hom.:

110

Cov.:

AF XY:

0.00334

AC XY:

2426

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0387

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0599

Gnomad4 SAS exome

AF:

0.00208

Gnomad4 FIN exome

AF:

0.00702

Gnomad4 NFE exome

AF:

0.000183

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.00499

AC:

759

AN:

152252

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

416

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.0188

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0561

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00652

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.000794

Hom.:

Bravo

AF:

0.00736

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00964

AC:

1170

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.000273

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:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

BMS1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 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

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.59

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.91

MPC

0.47

ClinPred

0.045

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.79

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