rs6025468

Variant names:

• chr20-57255095-A-G
• rs6025468
• NM_001719.3:c.418+10610T>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.418+10610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,040 control chromosomes in the GnomAD database, including 3,807 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 0.22 (3807 hom., cov: 31)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.418+10610T>C		intron_variant	Intron 1 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.418+10610T>C		intron_variant	Intron 1 of 6	1	NM_001719.3	ENSP00000379204.3
BMP7	ENST00000450594.6	c.418+10610T>C		intron_variant	Intron 1 of 5	2		ENSP00000398687.2
BMP7	ENST00000395864.7	c.418+10610T>C		intron_variant	Intron 1 of 5	5		ENSP00000379205.3
BMP7	ENST00000433911.1	c.73+10610T>C		intron_variant	Intron 1 of 6	5		ENSP00000390814.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32879 AN: 151922 Hom.: 3797 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.217 AC: 32931 AN: 152040 Hom.: 3807 Cov.: 31 AF XY: 0.219 AC XY: 16296 AN XY: 74310

African (AFR) AF: 0.286 AC: 11846 AN: 41432

American (AMR) AF: 0.196 AC: 2996 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 534 AN: 3466

East Asian (EAS) AF: 0.0134 AC: 69 AN: 5168

South Asian (SAS) AF: 0.194 AC: 934 AN: 4820

European-Finnish (FIN) AF: 0.235 AC: 2480 AN: 10564

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13526 AN: 67978

Other (OTH) AF: 0.199 AC: 420 AN: 2114

Alfa AF: 0.199 Hom.: 13650

Bravo AF: 0.214

Asia WGS AF: 0.103 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.60
PhyloP100		-0.53
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: rs6025468; hg19: chr20-55830151;