rs16980799

Variant names:

• chr20-57171260-T-C
• rs16980799
• NM_001719.3:c.1147-152A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001719.3(BMP7):​c.1147-152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,124,550 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (26 hom.)
• Consequence: BMP7 NM_001719.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.15
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-57171260-T-C is Benign according to our data. Variant chr20-57171260-T-C is described in ClinVar as [Benign]. Clinvar id is 1273116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2212/152342) while in subpopulation AFR AF = 0.0503 (2089/41566). AF 95% confidence interval is 0.0485. There are 50 homozygotes in GnomAd4. There are 1038 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2212 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BMP7	NM_001719.3	c.1147-152A>G		intron_variant	Intron 6 of 6	ENST00000395863.8	NP_001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BMP7	ENST00000395863.8	c.1147-152A>G		intron_variant	Intron 6 of 6	1	NM_001719.3	ENSP00000379204.3
BMP7	ENST00000395864.7	c.949-152A>G		intron_variant	Intron 5 of 5	5		ENSP00000379205.3
BMP7	ENST00000460817.5	n.647-152A>G		intron_variant	Intron 5 of 5	3
BMP7	ENST00000476877.1	n.391-152A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2210 AN: 152224 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00150 AC: 1454 AN: 972208 Hom.: 26 AF XY: 0.00119 AC XY: 591 AN XY: 495860

African (AFR) AF: 0.0479 AC: 1114 AN: 23256

American (AMR) AF: 0.00259 AC: 91 AN: 35112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22340

East Asian (EAS) AF: 0.00 AC: 0 AN: 33850

South Asian (SAS) AF: 0.000272 AC: 19 AN: 69948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42432

Middle Eastern (MID) AF: 0.00235 AC: 11 AN: 4688

European-Non Finnish (NFE) AF: 0.0000876 AC: 61 AN: 696372

Other (OTH) AF: 0.00357 AC: 158 AN: 44210

GnomAD4 genome AF: 0.0145 AC: 2212 AN: 152342 Hom.: 50 Cov.: 33 AF XY: 0.0139 AC XY: 1038 AN XY: 74498

African (AFR) AF: 0.0503 AC: 2089 AN: 41566

American (AMR) AF: 0.00542 AC: 83 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68032

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

Alfa AF: 0.0185 Hom.: 6

Bravo AF: 0.0161

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.40
DANN	Benign	0.66
PhyloP100		-2.1
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: rs16980799; hg19: chr20-55746316;