rs11597689

Positions:

• chr10-86889419-G-A

Variant summary

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

The NM_004329.3(BMPR1A):​c.68-643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 152,378 control chromosomes in the GnomAD database, including 384 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 0.068 (384 hom., cov: 33)
  • Exomes 𝑓: 0.087 (0 hom.)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

Genes affected

BMPR1A (HGNC:1076): (bone morphogenetic protein receptor type 1A) The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF-beta superfamily. TGF-betas and activins transduce their signals through the formation of heteromeric complexes with 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. [provided by RefSeq, Jul 2008]

BMPR1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMPR1A	NM_004329.3	c.68-643G>A		intron_variant		ENST00000372037.8	NP_004320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000372037.8	c.68-643G>A		intron_variant		1	NM_004329.3	ENSP00000361107.2

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10280 AN: 152110 Hom.: 383 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0867 AC: 13 AN: 150 Hom.: 0 AF XY: 0.0625 AC XY: 6 AN XY: 96

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0833

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0714

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0932

GnomAD4 genome AF: 0.0675 AC: 10278 AN: 152228 Hom.: 384 Cov.: 33 AF XY: 0.0675 AC XY: 5019 AN XY: 74408

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.0467

Gnomad4 ASJ AF: 0.0986

Gnomad4 EAS AF: 0.0713

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0609

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0727 Hom.: 601

Bravo AF: 0.0639

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.47

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: rs11597689; hg19: chr10-88649176;