10-86758698-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004329.3(BMPR1A):c.-268+1779T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0871 in 152,270 control chromosomes in the GnomAD database, including 1,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (1499 hom., cov: 33)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.130

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-86758698-T-G is Benign according to our data. Variant chr10-86758698-T-G is described in ClinVar as [Benign]. Clinvar id is 1294599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1A	NM_004329.3	c.-268+1779T>G		intron_variant		ENST00000372037.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-268+1779T>G		intron_variant		1	NM_004329.3	P1

Frequencies

GnomAD3 genomes AF: 0.0870 AC: 13237 AN: 152152 Hom.: 1496 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0372

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0871 AC: 13269 AN: 152270 Hom.: 1499 Cov.: 33 AF XY: 0.0843 AC XY: 6275 AN XY: 74470

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.00752 Hom.: 8

Bravo AF: 0.0987

Asia WGS AF: 0.0410 AC: 143 AN: 3478

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

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.4
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7072166; hg19: chr10-88518455;