rs61733436

Variant names:

• chr20-57183873-C-T
• rs61733436
• NM_001719.3:c.807G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-57183873-C-T
• chr20-57183873-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001719.3(BMP7):​c.807G>A​(p.Gly269Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,614,124 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 33)
  • Exomes 𝑓: 0.015 (187 hom.)
• Consequence: BMP7 NM_001719.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.201
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.031).
• BP6: Variant 20-57183873-C-T is Benign according to our data. Variant chr20-57183873-C-T is described in ClinVar as Benign. ClinVar VariationId is 2037439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.201 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0109 (1663/152314) while in subpopulation SAS AF = 0.0222 (107/4828). AF 95% confidence interval is 0.0188. There are 12 homozygotes in GnomAd4. There are 797 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1663 AD gene.

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.807G>A	p.Gly269Gly	synonymous	Exon 4 of 7	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.807G>A	p.Gly269Gly	synonymous	Exon 4 of 7	ENSP00000379204.3	P18075
	BMP7	ENST00000450594.6	TSL:2	c.807G>A	p.Gly269Gly	synonymous	Exon 4 of 6	ENSP00000398687.2	B1AL00
	BMP7	ENST00000433911.1	TSL:5	c.570G>A	p.Gly190Gly	synonymous	Exon 5 of 7	ENSP00000390814.1	H0Y4B5

Frequencies

GnomAD3 genomes AF: 0.0109 AC: 1663 AN: 152196 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0129 AC: 3234 AN: 251274 AF XY: 0.0143

Gnomad AFR exome AF: 0.00283

Gnomad AMR exome AF: 0.00879

Gnomad ASJ exome AF: 0.0210

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00857

Gnomad NFE exome AF: 0.0148

Gnomad OTH exome AF: 0.0140

GnomAD4 exome AF: 0.0148 AC: 21580 AN: 1461810 Hom.: 187 Cov.: 33 AF XY: 0.0152 AC XY: 11084 AN XY: 727212

African (AFR) AF: 0.00242 AC: 81 AN: 33480

American (AMR) AF: 0.00892 AC: 399 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 505 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0237 AC: 2048 AN: 86258

European-Finnish (FIN) AF: 0.00877 AC: 468 AN: 53344

Middle Eastern (MID) AF: 0.0236 AC: 136 AN: 5768

European-Non Finnish (NFE) AF: 0.0154 AC: 17109 AN: 1112008

Other (OTH) AF: 0.0138 AC: 832 AN: 60394

GnomAD4 genome AF: 0.0109 AC: 1663 AN: 152314 Hom.: 12 Cov.: 33 AF XY: 0.0107 AC XY: 797 AN XY: 74476

African (AFR) AF: 0.00248 AC: 103 AN: 41564

American (AMR) AF: 0.0142 AC: 218 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4828

European-Finnish (FIN) AF: 0.00659 AC: 70 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0152 AC: 1036 AN: 68028

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0139 Hom.: 41

Bravo AF: 0.0109

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0183

EpiControl AF: 0.0165

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.4
DANN	Benign	0.64
PhyloP100		0.20
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs61733436; hg19: chr20-55758929;