chr4-95033811-T-G

Variant names:

• chr4-95033811-T-G
• rs1434546
• NM_001203.3:c.-18+37677T>G

Variant summary

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

The NM_001203.3(BMPR1B):​c.-18+37677T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,088 control chromosomes in the GnomAD database, including 39,320 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 0.70 (39320 hom., cov: 33)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 1 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: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• acromesomelic dysplasia 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.846 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1B	NM_001203.3	MANE Select	c.-18+37677T>G		intron	N/A	NP_001194.1	O00238-1
	BMPR1B	NM_001256792.2		c.-18+37427T>G		intron	N/A	NP_001243721.1	O00238-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1B	ENST00000515059.6	TSL:1 MANE Select	c.-18+37677T>G		intron	N/A	ENSP00000426617.1	O00238-1
	BMPR1B	ENST00000512312.5	TSL:1	c.-18+37427T>G		intron	N/A	ENSP00000425444.1	O00238-1
	BMPR1B	ENST00000873516.1		c.-18+37427T>G		intron	N/A	ENSP00000543575.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106847 AN: 151970 Hom.: 39305 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.703 AC: 106904 AN: 152088 Hom.: 39320 Cov.: 33 AF XY: 0.705 AC XY: 52434 AN XY: 74340

African (AFR) AF: 0.453 AC: 18785 AN: 41478

American (AMR) AF: 0.793 AC: 12092 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2604 AN: 3468

East Asian (EAS) AF: 0.867 AC: 4481 AN: 5170

South Asian (SAS) AF: 0.828 AC: 3989 AN: 4820

European-Finnish (FIN) AF: 0.733 AC: 7756 AN: 10576

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54693 AN: 68002

Other (OTH) AF: 0.703 AC: 1486 AN: 2114

Alfa AF: 0.776 Hom.: 74441

Bravo AF: 0.694

Asia WGS AF: 0.788 AC: 2737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.78
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1434546; hg19: chr4-95954962;