Genetic Variant BMP7:c.1035+6G>A (chr20-57174925-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001719.3(BMP7):c.1035+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,610,326 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 12 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 9 hom. )

Consequence

BMP7
NM_001719.3 splice_region, intron

Scores

Splicing: ADA: 0.0001019

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.339

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 20-57174925-C-T is Benign according to our data. Variant chr20-57174925-C-T is described in ClinVar as [Benign]. Clinvar id is 710158.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00585 (891/152338) while in subpopulation AFR AF = 0.0194 (806/41572). AF 95% confidence interval is 0.0183. There are 12 homozygotes in GnomAd4. There are 424 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 891 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3 link	c.1035+6G>A		splice_region_variant, 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.1035+6G>A		splice_region_variant, intron_variant	Intron 5 of 6	1	NM_001719.3	ENSP00000379204.3		P18075

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

888

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00158

AC:

391

AN:

247284

AF XY:

0.00122

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000320

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000738

AC:

1076

AN:

1457988

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

489

AN XY:

725334

show subpopulations

Gnomad4 AFR exome

AF:

0.0202

AC:

675

AN:

33384

Gnomad4 AMR exome

AF:

0.00166

AC:

AN:

44654

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26116

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39600

Gnomad4 SAS exome

AF:

0.0000233

AC:

AN:

85906

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

50846

Gnomad4 NFE exome

AF:

0.000200

AC:

222

AN:

1111580

Gnomad4 Remaining exome

AF:

0.00149

AC:

AN:

60304

Heterozygous variant carriers

111

167

222

278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00585

AC:

891

AN:

152338

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

424

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0194

AC:

0.019388

AN:

0.019388

Gnomad4 AMR

AF:

0.00418

AC:

0.00418137

AN:

0.00418137

Gnomad4 ASJ

AF:

0.000288

AC:

0.000288018

AN:

0.000288018

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000220

AC:

0.000220484

AN:

0.000220484

Gnomad4 OTH

AF:

0.00189

AC:

0.00189215

AN:

0.00189215

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00344

Hom.:

Bravo

AF:

0.00694

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.74

CADD

Benign

7.9

DANN

Benign

0.72

Mutation Taster

=100/0

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over