rs11597689

Variant names:

• chr10-86889419-G-A
• rs11597689
• NM_004329.3:c.68-643G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004329.3(BMPR1A):​c.68-643G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 152,378 control chromosomes in the GnomAD database, including 384 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 0.068 (384 hom., cov: 33)
  • Exomes 𝑓: 0.087 (0 hom.)
• Consequence: BMPR1A NM_004329.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 9 publications found

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]

RNU1-19P (HGNC:41945): (RNA, U1 small nuclear 19, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004329.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	NM_004329.3	MANE Select	c.68-643G>A		intron	N/A	NP_004320.2
	BMPR1A	NM_001406559.1		c.68-643G>A		intron	N/A	NP_001393488.1
	BMPR1A	NM_001406560.1		c.68-643G>A		intron	N/A	NP_001393489.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1A	ENST00000372037.8	TSL:1 MANE Select	c.68-643G>A		intron	N/A	ENSP00000361107.2	P36894
	BMPR1A	ENST00000926286.1		c.68-643G>A		intron	N/A	ENSP00000596345.1
	BMPR1A	ENST00000480152.3	TSL:3	c.68-643G>A		intron	N/A	ENSP00000483569.2	P36894

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10280 AN: 152110 Hom.: 383 Cov.: 33

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0469

Gnomad ASJ AF: 0.0986

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0867 AC: 13 AN: 150 Hom.: 0 AF XY: 0.0625 AC XY: 6 AN XY: 96

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.0833 AC: 1 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.0714 AC: 1 AN: 14

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0932 AC: 11 AN: 118

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0675 AC: 10278 AN: 152228 Hom.: 384 Cov.: 33 AF XY: 0.0675 AC XY: 5019 AN XY: 74408

African (AFR) AF: 0.0624 AC: 2593 AN: 41552

American (AMR) AF: 0.0467 AC: 714 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0986 AC: 342 AN: 3470

East Asian (EAS) AF: 0.0713 AC: 370 AN: 5188

South Asian (SAS) AF: 0.115 AC: 554 AN: 4816

European-Finnish (FIN) AF: 0.0609 AC: 645 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0715 AC: 4861 AN: 68018

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0718 Hom.: 737

Bravo AF: 0.0639

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.47
PhyloP100		0.046
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11597689; hg19: chr10-88649176;