10-86807279-A-G

Variant names:

• chr10-86807279-A-G
• rs2168730
• NM_004329.3:c.-267-31586A>G

Variant summary

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

The NM_004329.3(BMPR1A):​c.-267-31586A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,170 control chromosomes in the GnomAD database, including 4,790 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 0.22 (4790 hom., cov: 32)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.800
• Publications: 7 publications found

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 Gene-Disease associations (from GenCC):

• generalized juvenile polyposis/juvenile polyposis coli

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Genomics England PanelApp
• juvenile polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• polyposis syndrome, hereditary mixed, 2

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• hereditary mixed polyposis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital heart defects, multiple types

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1A	NM_004329.3	c.-267-31586A>G		intron_variant	Intron 1 of 12	ENST00000372037.8	NP_004320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-267-31586A>G		intron_variant	Intron 1 of 12	1	NM_004329.3	ENSP00000361107.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33382 AN: 152050 Hom.: 4785 Cov.: 32

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.219 AC: 33395 AN: 152170 Hom.: 4790 Cov.: 32 AF XY: 0.229 AC XY: 17000 AN XY: 74376

African (AFR) AF: 0.0776 AC: 3222 AN: 41546

American (AMR) AF: 0.279 AC: 4268 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3468

East Asian (EAS) AF: 0.639 AC: 3304 AN: 5172

South Asian (SAS) AF: 0.259 AC: 1249 AN: 4822

European-Finnish (FIN) AF: 0.336 AC: 3550 AN: 10574

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15930 AN: 67986

Other (OTH) AF: 0.232 AC: 490 AN: 2114

Alfa AF: 0.121 Hom.: 213

Bravo AF: 0.213

Asia WGS AF: 0.362 AC: 1255 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		0.80
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: rs2168730; hg19: chr10-88567036;