NM_004329.3:c.334-504C>T

Variant names:

• chr10-86899290-C-T
• rs10887666
• NM_004329.3:c.334-504C>T

Variant summary

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

The NM_004329.3(BMPR1A):​c.334-504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,228 control chromosomes in the GnomAD database, including 2,631 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 0.15 (2631 hom., cov: 32)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• 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: Genomics England PanelApp, Orphanet, Ambry Genetics
• juvenile polyposis syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	NM_004329.3	MANE Select	c.334-504C>T		intron	N/A	NP_004320.2
	BMPR1A	NM_001406559.1		c.334-504C>T		intron	N/A	NP_001393488.1
	BMPR1A	NM_001406560.1		c.334-504C>T		intron	N/A	NP_001393489.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	ENST00000372037.8	TSL:1 MANE Select	c.334-504C>T		intron	N/A	ENSP00000361107.2	P36894
	BMPR1A	ENST00000926286.1		c.334-504C>T		intron	N/A	ENSP00000596345.1
	BMPR1A	ENST00000480152.3	TSL:3	c.334-504C>T		intron	N/A	ENSP00000483569.2	P36894

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22320 AN: 152108 Hom.: 2630 Cov.: 32

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.147 AC: 22319 AN: 152228 Hom.: 2631 Cov.: 32 AF XY: 0.154 AC XY: 11472 AN XY: 74404

African (AFR) AF: 0.0598 AC: 2487 AN: 41564

American (AMR) AF: 0.194 AC: 2967 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3468

East Asian (EAS) AF: 0.666 AC: 3439 AN: 5166

South Asian (SAS) AF: 0.156 AC: 752 AN: 4820

European-Finnish (FIN) AF: 0.216 AC: 2282 AN: 10578

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9061 AN: 68028

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.142 Hom.: 4067

Bravo AF: 0.147

Asia WGS AF: 0.332 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.32
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: rs10887666; hg19: chr10-88659047;