chr10-86857014-G-A

Variant names:

• chr10-86857014-G-A
• rs10788528
• NM_004329.3:c.-153+18035G>A

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+18035G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,192 control chromosomes in the GnomAD database, including 2,693 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 (2693 hom., cov: 32)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMPR1A	NM_004329.3	c.-153+18035G>A		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+18035G>A		intron_variant	Intron 2 of 12	1	NM_004329.3	ENSP00000361107.2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22566 AN: 152074 Hom.: 2690 Cov.: 32

Gnomad AFR AF: 0.0604

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.148 AC: 22569 AN: 152192 Hom.: 2693 Cov.: 32 AF XY: 0.156 AC XY: 11610 AN XY: 74394

African (AFR) AF: 0.0604 AC: 2509 AN: 41524

American (AMR) AF: 0.208 AC: 3180 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3444 AN: 5176

South Asian (SAS) AF: 0.157 AC: 755 AN: 4822

European-Finnish (FIN) AF: 0.216 AC: 2287 AN: 10594

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9054 AN: 68008

Other (OTH) AF: 0.161 AC: 339 AN: 2112

Alfa AF: 0.134 Hom.: 219

Bravo AF: 0.150

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.20
PhyloP100		0.84
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: rs10788528; hg19: chr10-88616771;