10-86819603-C-T

Variant names:

• chr10-86819603-C-T
• rs7095025
• NM_004329.3:c.-267-19262C>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.-267-19262C>T 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 152,188 control chromosomes in the GnomAD database, including 4,793 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 (4793 hom., cov: 33)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.623 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.-267-19262C>T		intron	N/A	NP_004320.2
	BMPR1A	NM_001406559.1		c.-267-19262C>T		intron	N/A	NP_001393488.1
	BMPR1A	NM_001406560.1		c.-267-19262C>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.-267-19262C>T		intron	N/A	ENSP00000361107.2	P36894
	BMPR1A	ENST00000926286.1		c.-267-19262C>T		intron	N/A	ENSP00000596345.1
	BMPR1A	ENST00000480152.3	TSL:3	c.-372-19262C>T		intron	N/A	ENSP00000483569.2	P36894

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33385 AN: 152070 Hom.: 4788 Cov.: 33

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.219 AC: 33398 AN: 152188 Hom.: 4793 Cov.: 33 AF XY: 0.229 AC XY: 17016 AN XY: 74406

African (AFR) AF: 0.0776 AC: 3226 AN: 41550

American (AMR) AF: 0.278 AC: 4248 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.641 AC: 3311 AN: 5164

South Asian (SAS) AF: 0.260 AC: 1255 AN: 4826

European-Finnish (FIN) AF: 0.337 AC: 3559 AN: 10570

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

European-Non Finnish (NFE) AF: 0.234 AC: 15923 AN: 68002

Other (OTH) AF: 0.233 AC: 492 AN: 2112

Alfa AF: 0.234 Hom.: 2271

Bravo AF: 0.213

Asia WGS AF: 0.362 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.85
PhyloP100		0.17
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: rs7095025; hg19: chr10-88579360;