rs162315

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001719.3(BMP7):c.419-5403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.381 (AC=58,003) in the gnomAD database across 152,170 control chromosomes, including 14,683 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.716. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 14683 hom., cov: 33)

Consequence

BMP7
NM_001719.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.307

Publications

5 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
congenital anomaly of kidney and urinary tract
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
hypospadias
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
isolated craniosynostosis
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia
Mayer-Rokitansky-Kuster-Hauser syndrome
Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

BMP7 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001719.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7155 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001719.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.419-5403C>T		intron	N/A	NP_001710.1	P18075

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP7	ENST00000395863.8	TSL:1 MANE Select	c.419-5403C>T	intron	N/A	ENSP00000379204.3	P18075
BMP7	ENST00000450594.6	TSL:2	c.419-5403C>T	intron	N/A	ENSP00000398687.2	B1AL00
BMP7	ENST00000395864.7	TSL:5	c.419-5403C>T	intron	N/A	ENSP00000379205.3	B1AKZ9

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57917

AN:

152052

Hom.:

14661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.723

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.381

AC:

58003

AN:

152170

Hom.:

14683

Cov.:

AF XY:

0.374

AC XY:

27850

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.722

AC:

29981

AN:

41504

American (AMR)

AF:

0.363

AC:

5558

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

874

AN:

3466

East Asian (EAS)

AF:

0.333

AC:

1725

AN:

5180

South Asian (SAS)

AF:

0.211

AC:

1019

AN:

4828

European-Finnish (FIN)

AF:

0.201

AC:

2125

AN:

10584

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15626

AN:

67992

Other (OTH)

AF:

0.371

AC:

784

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1515

3030

4544

6059

7574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.412

AC:

109069

AN:

264690

Hom.:

28503

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.292

AC:

29138

AN:

99958

Hom.:

5580

Local populations

ABraOM SABE-WGS-1171

AF:

0.392

AC:

918

AN:

2342

Hom.:

201

ChinaMAP Phase 1

AF:

0.320

Denmark Genome

AF:

0.180

AC:

AN:

300

GenomeAsia100K

AF:

0.340

AC:

1182

AN:

3478

show subpopulations

Oceania

AF:

0.459

AC:

AN:

148

Hom.:

North-East Asia

AF:

0.229

AC:

161

AN:

702

Hom.:

South-East Asia

AF:

0.439

AC:

304

AN:

692

Hom.:

South Asia

AF:

0.292

AC:

423

AN:

1448

Hom.:

Africa

AF:

0.760

AC:

158

AN:

208

Hom.:

America

AF:

0.231

AC:

AN:

Hom.:

West Eurasia

AF:

0.246

AC:

AN:

228

Hom.:

Korea4K (4,157 Koreans)

AF:

0.248

AC:

1796

AN:

7232

Qatari Genome

AF:

0.364

AC:

AN:

176

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.229

AC:

28065

AN:

122818

Hom.:

3227

Turkish Variome

AF:

0.223

AC:

344

AN:

1546

Hom.:

UK10K

AF:

0.239

AC:

1804

AN:

7562

show subpopulations

TwinsUK

AF:

0.227

AC:

811

AN:

3574

ALSPAC

AF:

0.249

AC:

959

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.340

AC:

3050

AN:

8960

Hom.:

527

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

(source)

DANN

Benign

0.75

PhyloP100

-0.31

AlphaGenome AVI

Benign

0.62

(source)

GPN-Star LLR

-1.4

(source)

GPN-Star score

1.4

(source)

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

Pangolin (max)

Benign

0.0

(source)

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over