rs17480735

Variant names:

• chr20-57170429-G-A
• rs17480735
• NM_001719.3:c.*530C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-57170429-G-A
• chr20-57170429-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001719.3(BMP7):​c.*530C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 202,684 control chromosomes in the GnomAD database, including 501 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 0.062 (368 hom., cov: 33)
  • Exomes 𝑓: 0.070 (133 hom.)
• Consequence: BMP7 NM_001719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• Publications: 8 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0792 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.*530C>T		3_prime_UTR	Exon 7 of 7	NP_001710.1	A8K571

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.*530C>T		3_prime_UTR	Exon 7 of 7	ENSP00000379204.3	P18075
	BMP7	ENST00000395864.7	TSL:5	c.*530C>T		downstream_gene	N/A	ENSP00000379205.3	B1AKZ9

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9382 AN: 152128 Hom.: 368 Cov.: 33

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0452

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0382

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.0700 AC: 3532 AN: 50436 Hom.: 133 Cov.: 0 AF XY: 0.0684 AC XY: 1780 AN XY: 26018

African (AFR) AF: 0.0229 AC: 29 AN: 1268

American (AMR) AF: 0.0500 AC: 180 AN: 3600

Ashkenazi Jewish (ASJ) AF: 0.0830 AC: 86 AN: 1036

East Asian (EAS) AF: 0.0305 AC: 96 AN: 3146

South Asian (SAS) AF: 0.0634 AC: 402 AN: 6340

European-Finnish (FIN) AF: 0.0903 AC: 210 AN: 2326

Middle Eastern (MID) AF: 0.0872 AC: 15 AN: 172

European-Non Finnish (NFE) AF: 0.0775 AC: 2328 AN: 30056

Other (OTH) AF: 0.0746 AC: 186 AN: 2492

GnomAD4 genome AF: 0.0616 AC: 9381 AN: 152248 Hom.: 368 Cov.: 33 AF XY: 0.0617 AC XY: 4594 AN XY: 74438

African (AFR) AF: 0.0249 AC: 1035 AN: 41542

American (AMR) AF: 0.0452 AC: 691 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 357 AN: 3470

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5178

South Asian (SAS) AF: 0.0680 AC: 328 AN: 4824

European-Finnish (FIN) AF: 0.100 AC: 1065 AN: 10602

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0810 AC: 5509 AN: 68016

Other (OTH) AF: 0.0601 AC: 127 AN: 2114

Alfa AF: 0.0386 Hom.: 25

Bravo AF: 0.0559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17480735; hg19: chr20-55745485;