rs4811822

Variant names:

• chr20-57203913-C-T
• rs4811822
• NM_001719.3:c.612-1290G>A

Variant summary

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

The NM_001719.3(BMP7):​c.612-1290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,132 control chromosomes in the GnomAD database, including 15,831 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 0.44 (15831 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.612-1290G>A		intron_variant	Intron 2 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.612-1290G>A		intron_variant	Intron 2 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66986 AN: 152014 Hom.: 15822 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.468

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.441 AC: 67031 AN: 152132 Hom.: 15831 Cov.: 33 AF XY: 0.445 AC XY: 33108 AN XY: 74372

African (AFR) AF: 0.274 AC: 11361 AN: 41484

American (AMR) AF: 0.536 AC: 8198 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1896 AN: 3466

East Asian (EAS) AF: 0.251 AC: 1298 AN: 5170

South Asian (SAS) AF: 0.559 AC: 2692 AN: 4816

European-Finnish (FIN) AF: 0.491 AC: 5203 AN: 10596

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34836 AN: 67986

Other (OTH) AF: 0.471 AC: 993 AN: 2110

Alfa AF: 0.447 Hom.: 2044

Bravo AF: 0.432

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.82
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4811822; hg19: chr20-55778969;