Variant chr10-42791727-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BP4_StrongBP6

The NM_014753.4(BMS1):c.737C>T(p.Pro246Leu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BMS1
NM_014753.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.74

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 Likely_benign. Variant got -4 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.020526499).

BP6

Variant 10-42791727-C-T is Benign according to our data. Variant chr10-42791727-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043996.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMS1	NM_014753.4 linkuse as main transcript	c.737C>T	p.Pro246Leu	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.737C>T	p.Pro246Leu	missense_variant	6/23	1	NM_014753.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

310

AN:

151370

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00250

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00921

Gnomad SAS

AF:

0.00293

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00185

AC:

460

AN:

248770

Hom.:

AF XY:

0.00166

AC XY:

223

AN XY:

134564

show subpopulations

Gnomad AFR exome

AF:

0.00299

Gnomad AMR exome

AF:

0.00502

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00637

Gnomad SAS exome

AF:

0.00289

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.000823

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000830

AC:

1210

AN:

1457270

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

646

AN XY:

724914

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.00626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00646

Gnomad4 SAS exome

AF:

0.00304

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.00148

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00205

AC:

310

AN:

151486

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

153

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.00424

Gnomad4 AMR

AF:

0.00250

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00904

Gnomad4 SAS

AF:

0.00293

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00177

Hom.:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00436

AC:

530

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

BMS1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2020

This variant is classified as likely 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

0.70

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.66

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-8.9

REVEL

Uncertain

0.46

Sift

Uncertain

0.011

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.81

MVP

0.64

MPC

0.50

ClinPred

0.077

GERP RS

5.5

Varity_R

0.72

gMVP

0.73

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