10-42791700-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3 BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.73

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]

ACMG classification

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	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	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.: 11 Cov.: 32

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.: 57 AF XY: 0.00966 AC XY: 1310 AN XY: 135596

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.: 30 AF XY: 0.00334 AC XY: 2426 AN XY: 726990

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.: 11 Cov.: 32 AF XY: 0.00559 AC XY: 416 AN XY: 74430

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.: 0

Bravo AF: 0.00736

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00964 AC: 1170

Asia WGS AF: 0.0250 AC: 88 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	T
BayesDel_noAF	Pathogenic	0.23
Cadd	Pathogenic	29
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.91
MPC		0.47
ClinPred		0.045	T
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

Other links and lift over

dbSNP: rs2272881; hg19: chr10-43287148; COSMIC: COSV65733293;