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GeneBe

4-94757964-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001203.3(BMPR1B):c.-287C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0007 in 141,342 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 0.00069 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0018 ( 0 hom. )

Consequence

BMPR1B
NM_001203.3 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.162
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000688 (96/139630) while in subpopulation AMR AF= 0.00141 (20/14144). AF 95% confidence interval is 0.000936. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BMPR1BNM_001203.3 linkuse as main transcriptc.-287C>G 5_prime_UTR_variant 1/13 ENST00000515059.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BMPR1BENST00000515059.6 linkuse as main transcriptc.-287C>G 5_prime_UTR_variant 1/131 NM_001203.3 P4O00238-1

Frequencies

GnomAD3 genomes
AF:
0.000688
AC:
96
AN:
139552
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000186
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00142
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000442
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000987
Gnomad OTH
AF:
0.00158
GnomAD4 exome
AF:
0.00175
AC:
3
AN:
1712
Hom.:
0
Cov.:
0
AF XY:
0.00191
AC XY:
2
AN XY:
1046
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00393
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000688
AC:
96
AN:
139630
Hom.:
0
Cov.:
31
AF XY:
0.000622
AC XY:
42
AN XY:
67490
show subpopulations
Gnomad4 AFR
AF:
0.000185
Gnomad4 AMR
AF:
0.00141
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000443
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000987
Gnomad4 OTH
AF:
0.00157
Alfa
AF:
0.000693
Hom.:
0
Bravo
AF:
0.000831

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Brachydactyly Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.54
Cadd
Benign
17
Dann
Benign
0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1019586523; hg19: chr4-95679115; API