4-95107904-C-T

Variant names:

• chr4-95107904-C-T
• rs7661539
• NM_001203.3:c.143+3337C>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.143+3337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,718 control chromosomes in the GnomAD database, including 28,482 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 0.59 (28482 hom., cov: 31)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.143+3337C>T		intron_variant	Intron 4 of 12	ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.143+3337C>T		intron_variant	Intron 4 of 12	1	NM_001203.3	ENSP00000426617.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88821 AN: 151600 Hom.: 28485 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.586 AC: 88838 AN: 151718 Hom.: 28482 Cov.: 31 AF XY: 0.583 AC XY: 43261 AN XY: 74164

African (AFR) AF: 0.318 AC: 13144 AN: 41352

American (AMR) AF: 0.657 AC: 10005 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2042 AN: 5132

South Asian (SAS) AF: 0.691 AC: 3335 AN: 4824

European-Finnish (FIN) AF: 0.612 AC: 6452 AN: 10542

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49245 AN: 67872

Other (OTH) AF: 0.617 AC: 1295 AN: 2100

Alfa AF: 0.697 Hom.: 19120

Bravo AF: 0.569

Asia WGS AF: 0.517 AC: 1794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.40
PhyloP100		-0.94
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: rs7661539; hg19: chr4-96029055;