chr4-94961876-G-A

Position:

• chr4-94961876-G-A

Variant summary

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

The NM_001203.3(BMPR1B):​c.-112-34164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 151,968 control chromosomes in the GnomAD database, including 23,348 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 0.54 (23348 hom., cov: 32)
• Consequence: BMPR1B NM_001203.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1B	NM_001203.3	c.-112-34164G>A		intron_variant		ENST00000515059.6	NP_001194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR1B	ENST00000515059.6	c.-112-34164G>A		intron_variant		1	NM_001203.3	ENSP00000426617	P4

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82743 AN: 151850 Hom.: 23314 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.545 AC: 82820 AN: 151968 Hom.: 23348 Cov.: 32 AF XY: 0.542 AC XY: 40239 AN XY: 74282

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.555

Alfa AF: 0.522 Hom.: 3733

Bravo AF: 0.547

Asia WGS AF: 0.461 AC: 1602 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.25

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: rs7661049; hg19: chr4-95883027;