rs34970181

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS1

The NM_001203.3(BMPR1B):c.1112G>A(p.Arg371Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000933 in 1,613,874 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R371L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 1 hom. )

Consequence

BMPR1B
NM_001203.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:2O:1

Conservation

PhyloP100: 8.00

Publications

14 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: Labcorp Genetics (formerly Invitae), Orphanet, 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13577956).

BP6

Variant 4-95148783-G-A is Benign according to our data. Variant chr4-95148783-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 441001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000861 (131/152138) while in subpopulation SAS AF = 0.00187 (9/4816). AF 95% confidence interval is 0.000975. There are 0 homozygotes in GnomAd4. There are 69 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001203.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMPR1B	NM_001203.3	MANE Select	c.1112G>A	p.Arg371Gln	missense	Exon 11 of 13	NP_001194.1	O00238-1
BMPR1B	NM_001256793.2		c.1202G>A	p.Arg401Gln	missense	Exon 9 of 11	NP_001243722.1	O00238-2
BMPR1B	NM_001256792.2		c.1112G>A	p.Arg371Gln	missense	Exon 9 of 11	NP_001243721.1	O00238-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BMPR1B	ENST00000515059.6	TSL:1 MANE Select	c.1112G>A	p.Arg371Gln	missense	Exon 11 of 13	ENSP00000426617.1	O00238-1
BMPR1B	ENST00000394931.1	TSL:1	c.1112G>A	p.Arg371Gln	missense	Exon 8 of 10	ENSP00000378389.1	O00238-1
BMPR1B	ENST00000512312.5	TSL:1	c.1112G>A	p.Arg371Gln	missense	Exon 9 of 11	ENSP00000425444.1	O00238-1

Frequencies

GnomAD3 genomes

AF:

0.000862

AC:

131

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000994

AC:

250

AN:

251396

AF XY:

0.000935

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000955

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00120

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000941

AC:

1375

AN:

1461736

Hom.:

Cov.:

AF XY:

0.000898

AC XY:

653

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33468

American (AMR)

AF:

0.000827

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26128

East Asian (EAS)

AF:

0.000428

AC:

AN:

39696

South Asian (SAS)

AF:

0.00145

AC:

125

AN:

86254

European-Finnish (FIN)

AF:

0.000431

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000986

AC:

1096

AN:

1111904

Other (OTH)

AF:

0.000878

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

165

247

330

412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<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:

0.000861

AC:

131

AN:

152138

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41514

American (AMR)

AF:

0.000459

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5170

South Asian (SAS)

AF:

0.00187

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

68010

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

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:

0.00100

Hom.:

Bravo

AF:

0.000808

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00110

AC:

133

EpiCase

AF:

0.000873

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

BMPR1B-related disorder (1)

not provided (1)

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

Type A2 brachydactyly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.049

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.49

MutationAssessor

Benign

-0.070

PhyloP100

8.0

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.81

MVP

0.75

MPC

0.21

ClinPred

0.043

GERP RS

5.5

Varity_R

0.84

gMVP

0.85

Mutation Taster

=69/31

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

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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