rs6123678

Variant names:

• chr20-57210666-C-T
• rs6123678
• NM_001719.3:c.612-8043G>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.612-8043G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,152 control chromosomes in the GnomAD database, including 14,499 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 0.41 (14499 hom., cov: 33)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.612-8043G>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.612-8043G>A		intron_variant	Intron 2 of 6	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61833 AN: 152034 Hom.: 14495 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.407 AC: 61861 AN: 152152 Hom.: 14499 Cov.: 33 AF XY: 0.412 AC XY: 30633 AN XY: 74360

Gnomad4 AFR AF: 0.165 AC: 0.165207 AN: 0.165207

Gnomad4 AMR AF: 0.524 AC: 0.524189 AN: 0.524189

Gnomad4 ASJ AF: 0.539 AC: 0.538594 AN: 0.538594

Gnomad4 EAS AF: 0.250 AC: 0.249611 AN: 0.249611

Gnomad4 SAS AF: 0.558 AC: 0.558067 AN: 0.558067

Gnomad4 FIN AF: 0.487 AC: 0.486556 AN: 0.486556

Gnomad4 NFE AF: 0.507 AC: 0.507413 AN: 0.507413

Gnomad4 OTH AF: 0.452 AC: 0.451659 AN: 0.451659

Alfa AF: 0.432 Hom.: 1903

Bravo AF: 0.392

Asia WGS AF: 0.436 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.62
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

Publications

LitVar

Other links and lift over

dbSNP: rs6123678; hg19: chr20-55785722;