Genetic Variant BMP7:c.1036-341_1036-337delTTTAT (chr20-57173646-CATAAA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001719.3(BMP7):c.1036-341_1036-337delTTTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 384,742 control chromosomes in the GnomAD database, including 48,521 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 18186 hom., cov: 0)

Exomes 𝑓: 0.49 ( 30335 hom. )

Consequence

BMP7
NM_001719.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

Publications

0 publications found

Variant links:

Genes affected

BMP7 (HGNC:1074): (bone morphogenetic protein 7) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer, which plays a role in bone, kidney and brown adipose tissue development. Additionally, this protein induces ectopic bone formation and may promote fracture healing in human patients. [provided by RefSeq, Jul 2016]

BMP7 Gene-Disease associations (from GenCC):

multiple congenital anomalies/dysmorphic syndrome
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
hypospadias
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

BMP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 20-57173646-CATAAA-C is Benign according to our data. Variant chr20-57173646-CATAAA-C is described in ClinVar as [Benign]. Clinvar id is 1249651.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3 link	c.1036-341_1036-337delTTTAT		intron_variant	Intron 5 of 6	ENST00000395863.8	NP_001710.1	P18075A8K571

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8 link	c.1036-341_1036-337delTTTAT		intron_variant	Intron 5 of 6	1	NM_001719.3	ENSP00000379204.3		P18075

Frequencies

GnomAD3 genomes

AF:

0.488

AC:

73873

AN:

151278

Hom.:

18162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.542

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.487

Gnomad OTH

AF:

0.511

GnomAD4 exome

AF:

0.490

AC:

114384

AN:

233350

Hom.:

30335

AF XY:

0.503

AC XY:

61676

AN XY:

122652

show subpopulations

African (AFR)

AF:

0.479

AC:

3593

AN:

7502

American (AMR)

AF:

0.569

AC:

5817

AN:

10228

Ashkenazi Jewish (ASJ)

AF:

0.540

AC:

3645

AN:

6744

East Asian (EAS)

AF:

0.295

AC:

4053

AN:

13746

South Asian (SAS)

AF:

0.654

AC:

20543

AN:

31420

European-Finnish (FIN)

AF:

0.402

AC:

4446

AN:

11054

Middle Eastern (MID)

AF:

0.523

AC:

513

AN:

980

European-Non Finnish (NFE)

AF:

0.472

AC:

65419

AN:

138638

Other (OTH)

AF:

0.487

AC:

6355

AN:

13038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

2608

5216

7824

10432

13040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.488

AC:

73950

AN:

151392

Hom.:

18186

Cov.:

AF XY:

0.488

AC XY:

36081

AN XY:

73942

show subpopulations

African (AFR)

AF:

0.493

AC:

20342

AN:

41234

American (AMR)

AF:

0.542

AC:

8252

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1939

AN:

3458

East Asian (EAS)

AF:

0.305

AC:

1567

AN:

5132

South Asian (SAS)

AF:

0.637

AC:

3051

AN:

4788

European-Finnish (FIN)

AF:

0.413

AC:

4327

AN:

10482

Middle Eastern (MID)

AF:

0.500

AC:

144

AN:

288

European-Non Finnish (NFE)

AF:

0.487

AC:

33004

AN:

67778

Other (OTH)

AF:

0.514

AC:

1084

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1875

3751

5626

7502

9377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.482

Hom.:

2097

Bravo

AF:

0.494

Asia WGS

AF:

0.510

AC:

1777

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 29, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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.

20-57173646-CATAAA-C

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