Genetic Variant NM_014753.4:c.376C>T (chr10-42787176-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014753.4(BMS1):c.376C>T(p.Arg126Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000889 in 1,203,124 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R126H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

BMS1
NM_014753.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

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

BMS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 12 AD gene.

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.376C>T	p.Arg126Cys	missense	Exon 4 of 23	NP_055568.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMS1	ENST00000374518.6	TSL:1 MANE Select	c.376C>T	p.Arg126Cys	missense	Exon 4 of 23	ENSP00000363642.4	Q14692
BMS1	ENST00000877424.1		c.376C>T	p.Arg126Cys	missense	Exon 4 of 24	ENSP00000547483.1
BMS1	ENST00000966891.1		c.376C>T	p.Arg126Cys	missense	Exon 4 of 23	ENSP00000636950.1

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000142

AC:

AN:

224956

AF XY:

0.000137

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000628

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000904

AC:

AN:

1051066

Hom.:

Cov.:

AF XY:

0.0000887

AC XY:

AN XY:

540960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25448

American (AMR)

AF:

0.000576

AC:

AN:

43432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23576

East Asian (EAS)

AF:

0.00

AC:

AN:

37832

South Asian (SAS)

AF:

0.0000259

AC:

AN:

77292

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37682

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3352

European-Non Finnish (NFE)

AF:

0.0000860

AC:

AN:

755438

Other (OTH)

AF:

0.0000638

AC:

AN:

47014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41488

American (AMR)

AF:

0.000328

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000959

Hom.:

Bravo

AF:

0.000102

ExAC

AF:

0.000106

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Benign

0.10

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

4.4

PhyloP100

4.7

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-7.3

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.023

Polyphen

0.10

Vest4

0.86

MutPred

0.66

Loss of MoRF binding (P = 0.0235)

MVP

0.74

MPC

2.5

ClinPred

0.99

GERP RS

4.8

Varity_R

0.68

gMVP

0.84

Mutation Taster

=22/78

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over