10-42791631-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP3 BP4_Strong BP6_Very_Strong

The NM_014753.4(BMS1):c.641C>T(p.Ala214Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000761 in 1,445,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMS1 NM_014753.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.74

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 -11 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, Cadd, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PrimateAI [when BayesDel_noAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.015581638).
• BP6: Variant 10-42791631-C-T is Benign according to our data. Variant chr10-42791631-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 734056.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMS1	NM_014753.4	c.641C>T	p.Ala214Val	missense_variant	6/23	ENST00000374518.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMS1	ENST00000374518.6	c.641C>T	p.Ala214Val	missense_variant	6/23	1	NM_014753.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 190 AN: 151148 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00152

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00532

Gnomad SAS AF: 0.00209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000761 AC: 1100 AN: 1445700 Hom.: 0 Cov.: 30 AF XY: 0.000835 AC XY: 600 AN XY: 718662

Gnomad4 AFR exome AF: 0.00266

Gnomad4 AMR exome AF: 0.00462

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.00627

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000206

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00126 AC: 190 AN: 151264 Hom.: 0 Cov.: 32 AF XY: 0.00131 AC XY: 97 AN XY: 73982

Gnomad4 AFR AF: 0.00249

Gnomad4 AMR AF: 0.00152

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00533

Gnomad4 SAS AF: 0.00209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000817 Hom.: 0

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.00428 AC: 520

EpiCase AF: 0.000274

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely 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

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	0.98
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Pathogenic	4.1	H
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.62
MPC		0.49
ClinPred		0.11	T
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.78
gMVP		0.77

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: rs141772670; hg19: chr10-43287079; COSMIC: COSV65733845;