20-57177754-A-G

Variant names:

• chr20-57177754-A-G
• rs6014949
• NM_001719.3:c.959-2747T>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.959-2747T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,196 control chromosomes in the GnomAD database, including 22,584 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 0.54 (22584 hom., cov: 35)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	NM_001719.3	MANE Select	c.959-2747T>C		intron	N/A	NP_001710.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMP7	ENST00000395863.8	TSL:1 MANE Select	c.959-2747T>C		intron	N/A	ENSP00000379204.3
	BMP7	ENST00000463939.1	TSL:3	n.589T>C		non_coding_transcript_exon	Exon 3 of 3
	BMP7	ENST00000450594.6	TSL:2	c.959-2747T>C		intron	N/A	ENSP00000398687.2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81765 AN: 152072 Hom.: 22530 Cov.: 35

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

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) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.538 AC: 81889 AN: 152190 Hom.: 22584 Cov.: 35 AF XY: 0.536 AC XY: 39872 AN XY: 74408

African (AFR) AF: 0.655 AC: 27182 AN: 41520

American (AMR) AF: 0.564 AC: 8615 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1956 AN: 3472

East Asian (EAS) AF: 0.378 AC: 1956 AN: 5176

South Asian (SAS) AF: 0.648 AC: 3121 AN: 4820

European-Finnish (FIN) AF: 0.401 AC: 4253 AN: 10606

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33233 AN: 67986

Other (OTH) AF: 0.552 AC: 1167 AN: 2116

Alfa AF: 0.511 Hom.: 10294

Bravo AF: 0.551

Asia WGS AF: 0.566 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		0.65
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: rs6014949; hg19: chr20-55752810;