4-95099077-A-G

Variant names:

• chr4-95099077-A-G
• rs1560909
• NM_001203.3:c.-17-5331A>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.-17-5331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,150 control chromosomes in the GnomAD database, including 53,638 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 0.84 (53638 hom., cov: 31)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.859 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.-17-5331A>G		intron	N/A	NP_001194.1
	BMPR1B	NM_001256793.2		c.74-5331A>G		intron	N/A	NP_001243722.1
	BMPR1B	NM_001256792.2		c.-17-5331A>G		intron	N/A	NP_001243721.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1B	ENST00000515059.6	TSL:1 MANE Select	c.-17-5331A>G		intron	N/A	ENSP00000426617.1
	BMPR1B	ENST00000512312.5	TSL:1	c.-17-5331A>G		intron	N/A	ENSP00000425444.1
	BMPR1B	ENST00000440890.7	TSL:2	c.74-5331A>G		intron	N/A	ENSP00000401907.2

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127670 AN: 152032 Hom.: 53600 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.834

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

GnomAD4 genome AF: 0.840 AC: 127767 AN: 152150 Hom.: 53638 Cov.: 31 AF XY: 0.840 AC XY: 62455 AN XY: 74380

African (AFR) AF: 0.799 AC: 33169 AN: 41500

American (AMR) AF: 0.868 AC: 13283 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2870 AN: 3468

East Asian (EAS) AF: 0.868 AC: 4483 AN: 5166

South Asian (SAS) AF: 0.881 AC: 4246 AN: 4820

European-Finnish (FIN) AF: 0.809 AC: 8562 AN: 10580

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58340 AN: 68004

Other (OTH) AF: 0.830 AC: 1751 AN: 2110

Alfa AF: 0.852 Hom.: 91949

Bravo AF: 0.840

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.28
PhyloP100		-0.16
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: rs1560909; hg19: chr4-96020228;