rs4145993

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001203.3(BMPR1B):​c.-112-912T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,046 control chromosomes in the GnomAD database, including 40,645 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 40645 hom., cov: 31)

Consequence

BMPR1B
NM_001203.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.408

Publications

6 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BMPR1BNM_001203.3 linkc.-112-912T>C intron_variant Intron 2 of 12 ENST00000515059.6 NP_001194.1 O00238-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BMPR1BENST00000515059.6 linkc.-112-912T>C intron_variant Intron 2 of 12 1 NM_001203.3 ENSP00000426617.1 O00238-1
BMPR1BENST00000672698.1 linkc.-112-912T>C intron_variant Intron 2 of 12 ENSP00000500035.1 O00238-1

Frequencies

GnomAD3 genomes
AF:
0.720
AC:
109446
AN:
151928
Hom.:
40623
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.514
Gnomad AMI
AF:
0.896
Gnomad AMR
AF:
0.798
Gnomad ASJ
AF:
0.766
Gnomad EAS
AF:
0.864
Gnomad SAS
AF:
0.818
Gnomad FIN
AF:
0.732
Gnomad MID
AF:
0.691
Gnomad NFE
AF:
0.804
Gnomad OTH
AF:
0.721
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.720
AC:
109519
AN:
152046
Hom.:
40645
Cov.:
31
AF XY:
0.722
AC XY:
53648
AN XY:
74320
show subpopulations
African (AFR)
AF:
0.514
AC:
21303
AN:
41438
American (AMR)
AF:
0.799
AC:
12201
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.766
AC:
2661
AN:
3472
East Asian (EAS)
AF:
0.864
AC:
4464
AN:
5168
South Asian (SAS)
AF:
0.819
AC:
3940
AN:
4812
European-Finnish (FIN)
AF:
0.732
AC:
7741
AN:
10572
Middle Eastern (MID)
AF:
0.688
AC:
201
AN:
292
European-Non Finnish (NFE)
AF:
0.804
AC:
54676
AN:
67990
Other (OTH)
AF:
0.717
AC:
1515
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1467
2933
4400
5866
7333
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
834
1668
2502
3336
4170
<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:
0.740
Hom.:
5506
Bravo
AF:
0.714
Asia WGS
AF:
0.787
AC:
2735
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.8
DANN
Benign
0.55
PhyloP100
-0.41
Mutation Taster
=100/0
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

Publications

Other links and lift over

dbSNP: rs4145993; hg19: chr4-95916279; API