rs11097457

Variant names:

• chr4-95155662-A-G
• rs11097457
• NM_001203.3:c.*989A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-95155662-A-G
• chr4-95155662-A-C
• chr4-95155662-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001203.3(BMPR1B):​c.*989A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,436 control chromosomes in the GnomAD database, including 29,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (29975 hom., cov: 27)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: BMPR1B NM_001203.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.311
• Publications: 12 publications found

Genes affected

BMPR1B (HGNC:1077): (bone morphogenetic protein receptor type 1B) This gene encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of 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. Mutations in this gene have been associated with primary pulmonary hypertension. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

BMPR1B Gene-Disease associations (from GenCC):

• brachydactyly type A2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• acromesomelic dysplasia 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• brachydactyly

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• brachydactyly type A1D

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• brachydactyly type A1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acromesomelic dysplasia 2A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• acromesomelic dysplasia 2B

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• pulmonary arterial hypertension

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-95155662-A-G is Benign according to our data. Variant chr4-95155662-A-G is described in ClinVar as Benign. ClinVar VariationId is 350147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001203.3. 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
	BMPR1B	NM_001203.3	MANE Select	c.*989A>G		3_prime_UTR	Exon 13 of 13	NP_001194.1	O00238-1
	BMPR1B	NM_001256793.2		c.*989A>G		3_prime_UTR	Exon 11 of 11	NP_001243722.1	O00238-2
	BMPR1B	NM_001256792.2		c.*989A>G		3_prime_UTR	Exon 11 of 11	NP_001243721.1	O00238-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMPR1B	ENST00000515059.6	TSL:1 MANE Select	c.*989A>G		3_prime_UTR	Exon 13 of 13	ENSP00000426617.1	O00238-1
	BMPR1B	ENST00000873516.1		c.*989A>G		3_prime_UTR	Exon 12 of 12	ENSP00000543575.1
	BMPR1B	ENST00000440890.7	TSL:2	c.*989A>G		3_prime_UTR	Exon 11 of 11	ENSP00000401907.2	O00238-2

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94711 AN: 151318 Hom.: 29931 Cov.: 27

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

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

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.626 AC: 94810 AN: 151434 Hom.: 29975 Cov.: 27 AF XY: 0.624 AC XY: 46167 AN XY: 73944

African (AFR) AF: 0.697 AC: 28760 AN: 41246

American (AMR) AF: 0.694 AC: 10580 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2472 AN: 3462

East Asian (EAS) AF: 0.430 AC: 2199 AN: 5112

South Asian (SAS) AF: 0.480 AC: 2288 AN: 4768

European-Finnish (FIN) AF: 0.610 AC: 6384 AN: 10466

Middle Eastern (MID) AF: 0.748 AC: 217 AN: 290

European-Non Finnish (NFE) AF: 0.591 AC: 40072 AN: 67826

Other (OTH) AF: 0.651 AC: 1370 AN: 2106

Alfa AF: 0.601 Hom.: 15217

Bravo AF: 0.640

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Brachydactyly (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.41
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11097457; hg19: chr4-96076813;