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. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• aplasia cutis congenita

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014753.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMS1	NM_014753.4	MANE Select	c.1955A>G	p.Lys652Arg	missense	Exon 10 of 23	NP_055568.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMS1	ENST00000374518.6	TSL:1 MANE Select	c.1955A>G	p.Lys652Arg	missense	Exon 10 of 23	ENSP00000363642.4	Q14692
	BMS1	ENST00000877424.1		c.1955A>G	p.Lys652Arg	missense	Exon 10 of 24	ENSP00000547483.1
	BMS1	ENST00000966891.1		c.1955A>G	p.Lys652Arg	missense	Exon 10 of 23	ENSP00000636950.1

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

GnomAD2 exomes AF: 0.187 AC: 45772 AN: 245162 AF XY: 0.186

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 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

African (AFR) AF: 0.180 AC: 5935 AN: 33028

American (AMR) AF: 0.232 AC: 10144 AN: 43714

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5082 AN: 25938

East Asian (EAS) AF: 0.240 AC: 9518 AN: 39642

South Asian (SAS) AF: 0.181 AC: 15400 AN: 84884

European-Finnish (FIN) AF: 0.221 AC: 11808 AN: 53374

Middle Eastern (MID) AF: 0.228 AC: 1311 AN: 5742

European-Non Finnish (NFE) AF: 0.156 AC: 173427 AN: 1109930

Other (OTH) AF: 0.170 AC: 10229 AN: 60118

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

African (AFR) AF: 0.180 AC: 7468 AN: 41534

American (AMR) AF: 0.220 AC: 3367 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 675 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1031 AN: 5168

South Asian (SAS) AF: 0.183 AC: 883 AN: 4820

European-Finnish (FIN) AF: 0.236 AC: 2494 AN: 10580

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10803 AN: 68004

Other (OTH) AF: 0.201 AC: 425 AN: 2116

Alfa AF: 0.169 Hom.: 9966

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 v4.9

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
PhyloP100		0.70
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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