Genetic Variant NM_001719.3:c.612-12468A>G (chr20-57215091-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001719.3(BMP7):c.612-12468A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,240 control chromosomes in the GnomAD database, including 35,846 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35835 hom., cov: 34)

Exomes 𝑓: 0.65 ( 11 hom. )

Consequence

BMP7
NM_001719.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.498

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 links:

BMP7-AS1 (HGNC:40096): (BMP7 antisense RNA 1)

BMP7-AS1 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.612-12468A>G		intron	N/A	NP_001710.1	A8K571
	BMP7-AS1	NR_110631.1		n.653+143T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BMP7	ENST00000395863.8	TSL:1 MANE Select	c.612-12468A>G	intron	N/A	ENSP00000379204.3	P18075
BMP7	ENST00000450594.6	TSL:2	c.612-12468A>G	intron	N/A	ENSP00000398687.2	B1AL00
BMP7	ENST00000395864.7	TSL:5	c.612-12468A>G	intron	N/A	ENSP00000379205.3	B1AKZ9

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102424

AN:

152068

Hom.:

35794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.866

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.585

Gnomad MID

AF:

0.672

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.648

AC:

AN:

Hom.:

AF XY:

0.588

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.650

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.674

AC:

102530

AN:

152186

Hom.:

35835

Cov.:

AF XY:

0.670

AC XY:

49869

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.866

AC:

35964

AN:

41522

American (AMR)

AF:

0.652

AC:

9985

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2071

AN:

3468

East Asian (EAS)

AF:

0.346

AC:

1790

AN:

5176

South Asian (SAS)

AF:

0.633

AC:

3054

AN:

4828

European-Finnish (FIN)

AF:

0.585

AC:

6193

AN:

10590

Middle Eastern (MID)

AF:

0.668

AC:

195

AN:

292

European-Non Finnish (NFE)

AF:

0.607

AC:

41298

AN:

67988

Other (OTH)

AF:

0.669

AC:

1413

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1654

3308

4963

6617

8271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.628

Hom.:

49518

Bravo

AF:

0.682

Asia WGS

AF:

0.536

AC:

1861

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.3

(source)

DANN

Benign

0.65

PhyloP100

-0.50

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over