4-94975193-G-C

Position:

• chr4-94975193-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001203.3(BMPR1B):​c.-112-20847G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,760 control chromosomes in the GnomAD database, including 27,129 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 (27129 hom., cov: 30)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.-112-20847G>C		intron_variant		ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-112-20847G>C		intron_variant		1	NM_001203.3	ENSP00000426617.1
BMPR1B	ENST00000672698.1	c.-185+46G>C		intron_variant				ENSP00000500035.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89509 AN: 151642 Hom.: 27118 Cov.: 30

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.590 AC: 89556 AN: 151760 Hom.: 27129 Cov.: 30 AF XY: 0.592 AC XY: 43875 AN XY: 74138

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.554

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.574

Alfa AF: 0.510 Hom.: 1503

Bravo AF: 0.589

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs2120834; hg19: chr4-95896344;