NM_001719.3:c.1146+192G>A

Variant names:

• chr20-57173008-C-T
• rs73914107
• NM_001719.3:c.1146+192G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001719.3(BMP7):​c.1146+192G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00617 in 662,316 control chromosomes in the GnomAD database, including 116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (86 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (30 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.08
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 20-57173008-C-T is Benign according to our data. Variant chr20-57173008-C-T is described in ClinVar as Benign. ClinVar VariationId is 1286946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0625 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.1146+192G>A		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.1146+192G>A		intron	N/A	ENSP00000379204.3	P18075
	BMP7	ENST00000450594.6	TSL:2	c.*99G>A		3_prime_UTR	Exon 6 of 6	ENSP00000398687.2	B1AL00
	BMP7	ENST00000395864.7	TSL:5	c.948+192G>A		intron	N/A	ENSP00000379205.3	B1AKZ9

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2827 AN: 152190 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00681

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00245 AC: 1248 AN: 510008 Hom.: 30 Cov.: 5 AF XY: 0.00200 AC XY: 544 AN XY: 271604

African (AFR) AF: 0.0612 AC: 853 AN: 13930

American (AMR) AF: 0.00402 AC: 109 AN: 27096

Ashkenazi Jewish (ASJ) AF: 0.00171 AC: 29 AN: 16994

East Asian (EAS) AF: 0.00 AC: 0 AN: 31530

South Asian (SAS) AF: 0.000387 AC: 21 AN: 54286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37204

Middle Eastern (MID) AF: 0.00582 AC: 13 AN: 2232

European-Non Finnish (NFE) AF: 0.000251 AC: 75 AN: 298478

Other (OTH) AF: 0.00524 AC: 148 AN: 28258

GnomAD4 genome AF: 0.0186 AC: 2836 AN: 152308 Hom.: 86 Cov.: 33 AF XY: 0.0183 AC XY: 1366 AN XY: 74480

African (AFR) AF: 0.0645 AC: 2682 AN: 41550

American (AMR) AF: 0.00680 AC: 104 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68042

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.0166 Hom.: 12

Bravo AF: 0.0205

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.43
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs73914107; hg19: chr20-55748064;