10-86847194-C-T

Variant names:

• chr10-86847194-C-T
• rs2354354
• NM_004329.3:c.-153+8215C>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.-153+8215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,850 control chromosomes in the GnomAD database, including 13,634 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 0.41 (13634 hom., cov: 31)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.467
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1A	NM_004329.3	c.-153+8215C>T		intron_variant	Intron 2 of 12	ENST00000372037.8	NP_004320.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-153+8215C>T		intron_variant	Intron 2 of 12	1	NM_004329.3	ENSP00000361107.2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61807 AN: 151734 Hom.: 13592 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.408 AC: 61890 AN: 151850 Hom.: 13634 Cov.: 31 AF XY: 0.413 AC XY: 30672 AN XY: 74190

African (AFR) AF: 0.541 AC: 22418 AN: 41404

American (AMR) AF: 0.372 AC: 5669 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1422 AN: 3466

East Asian (EAS) AF: 0.668 AC: 3447 AN: 5160

South Asian (SAS) AF: 0.389 AC: 1871 AN: 4810

European-Finnish (FIN) AF: 0.449 AC: 4722 AN: 10524

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21161 AN: 67922

Other (OTH) AF: 0.399 AC: 843 AN: 2114

Alfa AF: 0.279 Hom.: 995

Bravo AF: 0.413

Asia WGS AF: 0.491 AC: 1708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.99
DANN	Benign	0.44
PhyloP100		-0.47
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: rs2354354; hg19: chr10-88606951;