NM_014753.4:c.1955A>G

Variant names:

• chr10-42797199-A-G
• rs787795
• NM_014753.4:c.1955A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014753.4(BMS1):​c.1955A>G​(p.Lys652Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,608,574 control chromosomes in the GnomAD database, including 23,604 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2583 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21021 hom.)
• Consequence: BMS1 NM_014753.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001596868).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMS1	NM_014753.4	c.1955A>G	p.Lys652Arg	missense_variant	Exon 10 of 23	ENST00000374518.6	NP_055568.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMS1	ENST00000374518.6	c.1955A>G	p.Lys652Arg	missense_variant	Exon 10 of 23	1	NM_014753.4	ENSP00000363642.4

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27380 AN: 152086 Hom.: 2584 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.187 AC: 45772 AN: 245162 Hom.: 4459 AF XY: 0.186 AC XY: 24714 AN XY: 133140

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.230

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.198

Gnomad SAS exome AF: 0.183

Gnomad FIN exome AF: 0.226

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.167 AC: 242854 AN: 1456370 Hom.: 21021 Cov.: 33 AF XY: 0.167 AC XY: 121025 AN XY: 723954

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.170

GnomAD4 genome AF: 0.180 AC: 27378 AN: 152204 Hom.: 2583 Cov.: 33 AF XY: 0.184 AC XY: 13700 AN XY: 74390

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.201

Alfa AF: 0.167 Hom.: 5350

Bravo AF: 0.180

TwinsUK AF: 0.153 AC: 568

ALSPAC AF: 0.151 AC: 581

ESP6500AA AF: 0.169 AC: 724

ESP6500EA AF: 0.162 AC: 1381

ExAC AF: 0.182 AC: 22084

Asia WGS AF: 0.179 AC: 620 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.060
Sift	Benign	0.30	T
Sift4G	Benign	0.48	T
Polyphen		0.0010	B
Vest4		0.055
MPC		0.10
ClinPred		0.0021	T
GERP RS		2.6
Varity_R		0.024
gMVP		0.067

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: rs787795; hg19: chr10-43292647; COSMIC: COSV65733907;