4-95104504-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001256793.2(BMPR1B):c.170C>G(p.Pro57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,362 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

BMPR1B
NM_001256793.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 3.40

Publications

0 publications found

Variant links:

Genes affected

BMPR1B (HGNC:1077): (bone morphogenetic protein receptor type 1B) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 2 different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

BMPR1B Gene-Disease associations (from GenCC):

brachydactyly type A2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
acromesomelic dysplasia 3
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
brachydactyly
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
brachydactyly type A1D
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
brachydactyly type A1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
acromesomelic dysplasia 2A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
acromesomelic dysplasia 2B
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
pulmonary arterial hypertension
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

BMPR1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1905384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256793.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BMPR1B	NM_001203.3	MANE Select	c.80C>G	p.Pro27Arg	missense	Exon 4 of 13	NP_001194.1
BMPR1B	NM_001256793.2		c.170C>G	p.Pro57Arg	missense	Exon 2 of 11	NP_001243722.1
BMPR1B	NM_001256792.2		c.80C>G	p.Pro27Arg	missense	Exon 2 of 11	NP_001243721.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BMPR1B	ENST00000515059.6	TSL:1 MANE Select	c.80C>G	p.Pro27Arg	missense	Exon 4 of 13	ENSP00000426617.1
BMPR1B	ENST00000394931.1	TSL:1	c.80C>G	p.Pro27Arg	missense	Exon 1 of 10	ENSP00000378389.1
BMPR1B	ENST00000512312.5	TSL:1	c.80C>G	p.Pro27Arg	missense	Exon 2 of 11	ENSP00000425444.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251098

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461384

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111672

Other (OTH)

AF:

0.0000663

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.00000658

AC:

AN:

151978

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Pulmonary hypertension, primary, 3 (1)

Type A2 brachydactyly;C4225404:Acromesomelic dysplasia 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.16

Eigen

Benign

-0.16

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.066

MetaRNN

Benign

0.19

MetaSVM

Uncertain

-0.096

MutationAssessor

Benign

1.4

PhyloP100

3.4

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.40

Sift

Benign

0.39

Sift4G

Benign

0.52

Polyphen

0.024

Vest4

0.41

MutPred

0.32

Loss of glycosylation at P27 (P = 0.0291)

MVP

0.94

MPC

0.16

ClinPred

0.082

GERP RS

5.7

PromoterAI

0.024

Neutral

(source)

Varity_R

0.26

gMVP

0.56

Mutation Taster

=71/29

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over