rs17231982

Positions:

• chr10-86798092-C-G

Variant summary

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

The NM_004329.3(BMPR1A):​c.-267-40773C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,090 control chromosomes in the GnomAD database, including 526 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 0.075 (526 hom., cov: 32)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1A	NM_004329.3	c.-267-40773C>G		intron_variant		ENST00000372037.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-267-40773C>G		intron_variant		1	NM_004329.3	P1

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11454 AN: 151974 Hom.: 521 Cov.: 32

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0761

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

GnomAD4 genome AF: 0.0755 AC: 11477 AN: 152090 Hom.: 526 Cov.: 32 AF XY: 0.0765 AC XY: 5686 AN XY: 74354

Gnomad4 AFR AF: 0.0705

Gnomad4 AMR AF: 0.0582

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0808

Gnomad4 OTH AF: 0.0753

Alfa AF: 0.0762 Hom.: 64

Bravo AF: 0.0697

Asia WGS AF: 0.0510 AC: 177 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.9
DANN	Benign	0.87

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: rs17231982; hg19: chr10-88557849;