rs10375

Positions:

• chr20-57170625-A-G

Variant summary

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

The NM_001719.3(BMP7):​c.*334T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 352,400 control chromosomes in the GnomAD database, including 40,508 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 0.45 (16205 hom., cov: 32)
  • Exomes 𝑓: 0.48 (24303 hom.)
• Consequence: BMP7 NM_001719.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287

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 = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BMP7	NM_001719.3	c.*334T>C		3_prime_UTR_variant	7/7	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.*334T>C		3_prime_UTR_variant	7/7	1	NM_001719.3	ENSP00000379204	P1
BMP7	ENST00000395864.7	c.*334T>C		3_prime_UTR_variant	6/6	5		ENSP00000379205

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67666 AN: 151886 Hom.: 16207 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.480 AC: 96247 AN: 200396 Hom.: 24303 Cov.: 2 AF XY: 0.465 AC XY: 50340 AN XY: 108264

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.412

Gnomad4 ASJ exome AF: 0.443

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.578

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.483

GnomAD4 genome AF: 0.445 AC: 67672 AN: 152004 Hom.: 16205 Cov.: 32 AF XY: 0.447 AC XY: 33240 AN XY: 74296

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.443

Alfa AF: 0.495 Hom.: 14911

Bravo AF: 0.432

Asia WGS AF: 0.441 AC: 1530 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	0.53

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: rs10375; hg19: chr20-55745681; COSMIC: COSV67779492; COSMIC: COSV67779492;