20-57169849-G-C

Variant names:

• chr20-57169849-G-C
• rs6025417
• NM_001719.3:c.*1110C>G

Variant summary

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

The NM_001719.3(BMP7):​c.*1110C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,484 control chromosomes in the GnomAD database, including 15,108 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 0.43 (15108 hom., cov: 31)
  • Exomes 𝑓: 0.47 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMP7 NM_001719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 5 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 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.*1110C>G		3_prime_UTR	Exon 7 of 7	NP_001710.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.*1110C>G		3_prime_UTR	Exon 7 of 7	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65422 AN: 151364 Hom.: 15108 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.429

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.475 AC: 19 AN: 40 Hom.: 5 Cov.: 0 AF XY: 0.385 AC XY: 10 AN XY: 26

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.536 AC: 15 AN: 28

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.432 AC: 65433 AN: 151484 Hom.: 15108 Cov.: 31 AF XY: 0.434 AC XY: 32098 AN XY: 73964

African (AFR) AF: 0.262 AC: 10843 AN: 41368

American (AMR) AF: 0.421 AC: 6409 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3468

East Asian (EAS) AF: 0.675 AC: 3446 AN: 5108

South Asian (SAS) AF: 0.333 AC: 1602 AN: 4808

European-Finnish (FIN) AF: 0.572 AC: 5979 AN: 10460

Middle Eastern (MID) AF: 0.397 AC: 115 AN: 290

European-Non Finnish (NFE) AF: 0.503 AC: 34096 AN: 67736

Other (OTH) AF: 0.425 AC: 897 AN: 2110

Alfa AF: 0.338 Hom.: 935

Bravo AF: 0.421

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.092
DANN	Benign	0.29
PhyloP100		-3.1
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: rs6025417; hg19: chr20-55744905;