chr4-95149374-G-T

Variant names:

• chr4-95149374-G-T
• rs1970801
• NM_001203.3:c.1252+451G>T

Variant summary

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

The NM_001203.3(BMPR1B):​c.1252+451G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,978 control chromosomes in the GnomAD database, including 30,128 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 0.63 (30128 hom., cov: 32)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.56
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.1252+451G>T		intron_variant	Intron 11 of 12	ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.1252+451G>T		intron_variant	Intron 11 of 12	1	NM_001203.3	ENSP00000426617.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95044 AN: 151860 Hom.: 30082 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.626 AC: 95147 AN: 151978 Hom.: 30128 Cov.: 32 AF XY: 0.624 AC XY: 46355 AN XY: 74264

African (AFR) AF: 0.699 AC: 28962 AN: 41424

American (AMR) AF: 0.693 AC: 10587 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2475 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2217 AN: 5164

South Asian (SAS) AF: 0.477 AC: 2298 AN: 4814

European-Finnish (FIN) AF: 0.610 AC: 6426 AN: 10532

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40120 AN: 67988

Other (OTH) AF: 0.652 AC: 1376 AN: 2112

Alfa AF: 0.606 Hom.: 48587

Bravo AF: 0.640

Asia WGS AF: 0.509 AC: 1772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.069
DANN	Benign	0.34
PhyloP100		-3.6
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: rs1970801; hg19: chr4-96070525;