chr10-86758367-A-ATTT

Position:

• chr10-86758367-A-ATTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004329.3(BMPR1A):​c.-268+1463_-268+1465dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0098 (15 hom., cov: 0)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Likely 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-ATTT is Benign according to our data. Variant chr10-86758367-A-ATTT is described in ClinVar as [Likely_benign]. Clinvar id is 1702793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00979 (1380/141024) while in subpopulation NFE AF= 0.0139 (902/64724). AF 95% confidence interval is 0.0132. There are 15 homozygotes in gnomad4. There are 671 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1380 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMPR1A	NM_004329.3	c.-268+1463_-268+1465dup		intron_variant		ENST00000372037.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMPR1A	ENST00000372037.8	c.-268+1463_-268+1465dup		intron_variant		1	NM_004329.3	P1

Frequencies

GnomAD3 genomes AF: 0.00980 AC: 1381 AN: 140982 Hom.: 15 Cov.: 0

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.00535

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00474

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00350

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00680

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

GnomAD4 genome AF: 0.00979 AC: 1380 AN: 141024 Hom.: 15 Cov.: 0 AF XY: 0.00986 AC XY: 671 AN XY: 68040

Gnomad4 AFR AF: 0.00233

Gnomad4 AMR AF: 0.00534

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00454

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.00674

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 04, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

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;