rs11947569

Variant names:

• chr4-94835746-T-C
• rs11947569
• NM_001203.3:c.-182-40085T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001203.3(BMPR1B):​c.-182-40085T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,108 control chromosomes in the GnomAD database, including 3,494 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 0.21 (3494 hom., cov: 31)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1B	NM_001203.3	MANE Select	c.-182-40085T>C		intron	N/A	NP_001194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1B	ENST00000515059.6	TSL:1 MANE Select	c.-182-40085T>C		intron	N/A	ENSP00000426617.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31734 AN: 151990 Hom.: 3489 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0935

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31748 AN: 152108 Hom.: 3494 Cov.: 31 AF XY: 0.205 AC XY: 15220 AN XY: 74364

African (AFR) AF: 0.244 AC: 10099 AN: 41474

American (AMR) AF: 0.147 AC: 2243 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3466

East Asian (EAS) AF: 0.0937 AC: 485 AN: 5174

South Asian (SAS) AF: 0.238 AC: 1144 AN: 4816

European-Finnish (FIN) AF: 0.189 AC: 2003 AN: 10592

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14595 AN: 67994

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.212 Hom.: 964

Bravo AF: 0.203

Asia WGS AF: 0.183 AC: 632 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.75
PhyloP100		-0.66
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

Other links and lift over

dbSNP: rs11947569; hg19: chr4-95756897;