chr8-22195610-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006129.5(BMP1):c.1765+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,602,902 control chromosomes in the GnomAD database, including 127,440 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16955 hom., cov: 30)

Exomes 𝑓: 0.39 ( 110485 hom. )

Consequence

BMP1
NM_006129.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0340

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

osteogenesis imperfecta type 13
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
high bone mass osteogenesis imperfecta
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
osteogenesis imperfecta type 3
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

BMP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-22195610-T-C is Benign according to our data. Variant chr8-22195610-T-C is described in ClinVar as Benign. ClinVar VariationId is 674968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
BMP1	NM_006129.5 link	c.1765+23T>C	intron_variant	Intron 13 of 19	ENST00000306385.10	NP_006120.1
BMP1	NM_001199.4 link	c.1765+23T>C	intron_variant	Intron 13 of 15	ENST00000306349.13	NP_001190.1
BMP1	NR_033403.2 link	n.1836+23T>C	intron_variant	Intron 13 of 19
BMP1	NR_033404.2 link	n.1836+23T>C	intron_variant	Intron 13 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP1	ENST00000306385.10 link	c.1765+23T>C		intron_variant	Intron 13 of 19	1	NM_006129.5	ENSP00000305714.5
BMP1	ENST00000306349.13 link	c.1765+23T>C		intron_variant	Intron 13 of 15	1	NM_001199.4	ENSP00000306121.8

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69595

AN:

151656

Hom.:

16918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.425

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.446

GnomAD2 exomes

AF:

0.425

AC:

100276

AN:

236138

AF XY:

0.414

show subpopulations

Gnomad AFR exome

AF:

0.621

Gnomad AMR exome

AF:

0.542

Gnomad ASJ exome

AF:

0.399

Gnomad EAS exome

AF:

0.545

Gnomad FIN exome

AF:

0.414

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.410

GnomAD4 exome

AF:

0.385

AC:

558826

AN:

1451132

Hom.:

110485

Cov.:

AF XY:

0.384

AC XY:

277064

AN XY:

722008

show subpopulations

African (AFR)

AF:

0.619

AC:

20142

AN:

32558

American (AMR)

AF:

0.541

AC:

22953

AN:

42430

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

10216

AN:

25838

East Asian (EAS)

AF:

0.567

AC:

22126

AN:

39022

South Asian (SAS)

AF:

0.393

AC:

33375

AN:

84876

European-Finnish (FIN)

AF:

0.408

AC:

21349

AN:

52356

Middle Eastern (MID)

AF:

0.347

AC:

1804

AN:

5194

European-Non Finnish (NFE)

AF:

0.363

AC:

402715

AN:

1108980

Other (OTH)

AF:

0.403

AC:

24146

AN:

59878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17980

35959

53939

71918

89898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13082

26164

39246

52328

65410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.459

AC:

69678

AN:

151770

Hom.:

16955

Cov.:

AF XY:

0.462

AC XY:

34235

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.616

AC:

25519

AN:

41394

American (AMR)

AF:

0.489

AC:

7473

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

1394

AN:

3470

East Asian (EAS)

AF:

0.557

AC:

2863

AN:

5140

South Asian (SAS)

AF:

0.391

AC:

1881

AN:

4808

European-Finnish (FIN)

AF:

0.425

AC:

4454

AN:

10472

Middle Eastern (MID)

AF:

0.345

AC:

100

AN:

290

European-Non Finnish (NFE)

AF:

0.363

AC:

24680

AN:

67916

Other (OTH)

AF:

0.446

AC:

938

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1809

3618

5426

7235

9044

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.397

Hom.:

21271

Bravo

AF:

0.472

Asia WGS

AF:

0.510

AC:

1775

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 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. -

Osteogenesis imperfecta type 13

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

-0.90

CADD

Benign

0.27

(source)

DANN

Benign

0.33

PhyloP100

-0.034

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over