10-86758367-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004329.3(BMPR1A):c.-268+1465dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.048 (198 hom., cov: 0)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790

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 -10 ACMG points.

• BP6: Variant 10-86758367-A-AT is Benign according to our data. Variant chr10-86758367-A-AT is described in ClinVar as [Benign]. Clinvar id is 1235314.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1A	NM_004329.3	c.-268+1465dup		intron_variant		ENST00000372037.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-268+1465dup		intron_variant		1	NM_004329.3	P1

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 6827 AN: 140942 Hom.: 197 Cov.: 0

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.0181

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0227

Gnomad EAS AF: 0.00874

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0248

Gnomad MID AF: 0.0140

Gnomad NFE AF: 0.0430

Gnomad OTH AF: 0.0329

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

GnomAD4 genome AF: 0.0485 AC: 6834 AN: 140984 Hom.: 198 Cov.: 0 AF XY: 0.0477 AC XY: 3247 AN XY: 68022

Gnomad4 AFR AF: 0.0801

Gnomad4 AMR AF: 0.0339

Gnomad4 ASJ AF: 0.0227

Gnomad4 EAS AF: 0.00877

Gnomad4 SAS AF: 0.0236

Gnomad4 FIN AF: 0.0248

Gnomad4 NFE AF: 0.0430

Gnomad4 OTH AF: 0.0336

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs200528013; hg19: chr10-88518124;