20-57168849-T-C

Variant names:

• chr20-57168849-T-C
• rs12438
• NM_001719.3:c.*2110A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001719.3(BMP7):​c.*2110A>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 0.434 in 151,664 control chromosomes in the GnomAD database, including 15,299 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 (15298 hom., cov: 32)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: BMP7 NM_001719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.660

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.*2110A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863	c.*2110A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001719.3	ENSP00000379204.3

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65806 AN: 151532 Hom.: 15300 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.357 AC: 5 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.434 AC: 65813 AN: 151650 Hom.: 15298 Cov.: 32 AF XY: 0.437 AC XY: 32366 AN XY: 74114

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.684

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.426

Alfa AF: 0.482 Hom.: 36011

Bravo AF: 0.420

Asia WGS AF: 0.434 AC: 1508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.9
DANN	Benign	0.36

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: rs12438; hg19: chr20-55743905;