Genetic Variant NM_001719.3:c.1146+151delA (chr20-57173048-AT-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001719.3(BMP7):c.1146+151delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 745,990 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00096 ( 0 hom. )

Consequence

BMP7
NM_001719.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.309

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3 link	c.1146+151delA		intron_variant	Intron 6 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.1146+151delA		intron_variant	Intron 6 of 6	1	NM_001719.3	ENSP00000379204.3		P18075

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

238

AN:

151454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00540

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00240

GnomAD4 exome

AF:

0.000957

AC:

569

AN:

594424

Hom.:

Cov.:

AF XY:

0.000880

AC XY:

277

AN XY:

314924

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00597

AC:

AN:

15900

American (AMR)

AF:

0.000918

AC:

AN:

31596

Ashkenazi Jewish (ASJ)

AF:

0.000685

AC:

AN:

18978

East Asian (EAS)

AF:

0.000129

AC:

AN:

31082

South Asian (SAS)

AF:

0.000447

AC:

AN:

60362

European-Finnish (FIN)

AF:

0.000539

AC:

AN:

44568

Middle Eastern (MID)

AF:

0.00176

AC:

AN:

2834

European-Non Finnish (NFE)

AF:

0.000941

AC:

337

AN:

358112

Other (OTH)

AF:

0.00113

AC:

AN:

30992

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.298

Heterozygous variant carriers

158

236

315

394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00158

AC:

239

AN:

151566

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

110

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.00541

AC:

224

AN:

41396

American (AMR)

AF:

0.000394

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000590

AC:

AN:

67800

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00161

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism

(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

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NM_001719.3:c.1146+151delA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over