10-86922798-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004329.3(BMPR1A):c.1343-578G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,254 control chromosomes in the GnomAD database, including 4,712 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 0.24 (4712 hom., cov: 33)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1A	NM_004329.3	c.1343-578G>T		intron_variant		ENST00000372037.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1A	ENST00000372037.8	c.1343-578G>T		intron_variant		1	NM_004329.3	P1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35876 AN: 152136 Hom.: 4700 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.236 AC: 35902 AN: 152254 Hom.: 4712 Cov.: 33 AF XY: 0.232 AC XY: 17238 AN XY: 74450

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.241

Alfa AF: 0.260 Hom.: 7293

Bravo AF: 0.243

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.68
Dann	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs12765929; hg19: chr10-88682555;