rs6123679

Variant names:

• chr20-57216292-T-G
• rs6123679
• NM_001719.3:c.611+11937A>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.611+11937A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 152,254 control chromosomes in the GnomAD database, including 437 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 0.046 (437 hom., cov: 31)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.253 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.611+11937A>C		intron	N/A	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.611+11937A>C		intron	N/A	ENSP00000379204.3	P18075
	BMP7	ENST00000450594.6	TSL:2	c.611+11937A>C		intron	N/A	ENSP00000398687.2	B1AL00
	BMP7	ENST00000395864.7	TSL:5	c.611+11937A>C		intron	N/A	ENSP00000379205.3	B1AKZ9

Frequencies

GnomAD3 genomes AF: 0.0455 AC: 6922 AN: 152136 Hom.: 430 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0428

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0279

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0455 AC: 6933 AN: 152254 Hom.: 437 Cov.: 31 AF XY: 0.0494 AC XY: 3675 AN XY: 74434

African (AFR) AF: 0.0109 AC: 454 AN: 41552

American (AMR) AF: 0.132 AC: 2026 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3466

East Asian (EAS) AF: 0.265 AC: 1368 AN: 5168

South Asian (SAS) AF: 0.102 AC: 494 AN: 4826

European-Finnish (FIN) AF: 0.0428 AC: 454 AN: 10602

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0279 AC: 1899 AN: 68014

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0315 Hom.: 194

Bravo AF: 0.0510

Asia WGS AF: 0.207 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.64
PhyloP100		-0.019
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: rs6123679; hg19: chr20-55791348;