Genetic Variant BMP1:n.-170A>G (chr8-22165236-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000397814(BMP1):c.-170A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 752,056 control chromosomes in the GnomAD database, including 225,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 47540 hom., cov: 33)

Exomes 𝑓: 0.77 ( 177719 hom. )

Consequence

BMP1
ENST00000397814 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

BMP1 (HGNC:1067): (bone morphogenetic protein 1) This gene encodes a protein that is capable of inducing formation of cartilage in vivo. Although other bone morphogenetic proteins are members of the TGF-beta superfamily, this gene encodes a protein that is not closely related to other known growth factors. This gene is expressed as alternatively spliced variants that share an N-terminal protease domain but differ in their C-terminal region. [provided by RefSeq, Aug 2008]

BMP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-22165236-A-G is Benign according to our data. Variant chr8-22165236-A-G is described in ClinVar as [Benign]. Clinvar id is 362573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
BMP1	NM_006129.5 link	c.-170A>G	upstream_gene_variant	ENST00000306385.10	NP_006120.1	P13497-1
BMP1	NM_001199.4 link	c.-170A>G	upstream_gene_variant	ENST00000306349.13	NP_001190.1	P13497-2
BMP1	NR_033403.2 link	n.-136A>G	upstream_gene_variant
BMP1	NR_033404.2 link	n.-136A>G	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10 link	c.-170A>G		upstream_gene_variant		1	NM_006129.5	ENSP00000305714.5		P13497-1
BMP1	ENST00000306349.13 link	c.-170A>G		upstream_gene_variant		1	NM_001199.4	ENSP00000306121.8		P13497-2

Frequencies

GnomAD3 genomes

AF:

0.789

AC:

119833

AN:

151838

Hom.:

47489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.850

Gnomad AMI

AF:

0.787

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.635

Gnomad SAS

AF:

0.635

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.774

Gnomad OTH

AF:

0.798

GnomAD4 exome

AF:

0.768

AC:

460874

AN:

600110

Hom.:

177719

Cov.:

AF XY:

0.765

AC XY:

230779

AN XY:

301542

show subpopulations

Gnomad4 AFR exome

AF:

0.858

Gnomad4 AMR exome

AF:

0.820

Gnomad4 ASJ exome

AF:

0.831

Gnomad4 EAS exome

AF:

0.678

Gnomad4 SAS exome

AF:

0.647

Gnomad4 FIN exome

AF:

0.748

Gnomad4 NFE exome

AF:

0.777

Gnomad4 OTH exome

AF:

0.774

GnomAD4 genome

AF:

0.789

AC:

119933

AN:

151946

Hom.:

47540

Cov.:

AF XY:

0.785

AC XY:

58322

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.850

Gnomad4 AMR

AF:

0.811

Gnomad4 ASJ

AF:

0.830

Gnomad4 EAS

AF:

0.635

Gnomad4 SAS

AF:

0.635

Gnomad4 FIN

AF:

0.750

Gnomad4 NFE

AF:

0.773

Gnomad4 OTH

AF:

0.796

Alfa

AF:

0.775

Hom.:

5367

Bravo

AF:

0.802

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Interstitial lung disease 2

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pulmonary Surfactant Metabolism Dysfunction, Dominant

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Osteogenesis Imperfecta, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over