rs796563569
Variant names:
Your query was ambiguous. Multiple possible variants found:
- chr14-53949883-C-CA
- chr14-53949883-C-CAA
- chr14-53949883-C-CACT
- chr14-53949883-C-CAT
- chr14-53949883-C-CATT
- chr14-53949883-C-CATTT
- chr14-53949883-C-CATTTT
- chr14-53949883-C-CATTTTT
- chr14-53949883-C-CATTTTTT
- chr14-53949883-C-CATTTTTTT
- chr14-53949883-C-CATTTTTTTT
- chr14-53949883-C-CATTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
- chr14-53949883-C-CCAT
- chr14-53949883-C-CCATT
- chr14-53949883-C-CCT
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_001202.6(BMP4):c.*148_*149insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.016 ( 19 hom., cov: 0)
Exomes 𝑓: 0.12 ( 387 hom. )
Consequence
BMP4
NM_001202.6 3_prime_UTR
NM_001202.6 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -4.04
Publications
2 publications found
Genes affected
BMP4 (HGNC:1071): (bone morphogenetic protein 4) 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. This protein regulates heart development and adipogenesis. Mutations in this gene are associated with orofacial cleft and microphthalmia in human patients. The encoded protein may also be involved in the pathology of multiple cardiovascular diseases and human cancers. [provided by RefSeq, Jul 2016]
BMP4 Gene-Disease associations (from GenCC):
- BMP4-related ocular growth disorderInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- microphthalmia with brain and digit anomaliesInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- Stickler syndromeInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- renal agenesis, unilateralInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- orofacial cleft 11Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -5 ACMG points.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0155 (2088/134332) while in subpopulation AFR AF = 0.032 (1076/33666). AF 95% confidence interval is 0.0304. There are 19 homozygotes in GnomAd4. There are 1036 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAd4 at 19 AD,AR gene
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001202.6. 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 |
|---|---|---|---|---|---|---|---|---|---|
| BMP4 | NM_001202.6 | MANE Select | c.*148_*149insT | 3_prime_UTR | Exon 4 of 4 | NP_001193.2 | P12644 | ||
| BMP4 | NM_001347912.1 | c.*148_*149insT | 3_prime_UTR | Exon 4 of 4 | NP_001334841.1 | ||||
| BMP4 | NM_001347914.2 | c.*148_*149insT | 3_prime_UTR | Exon 3 of 3 | NP_001334843.1 | P12644 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BMP4 | ENST00000245451.9 | TSL:1 MANE Select | c.*148_*149insT | 3_prime_UTR | Exon 4 of 4 | ENSP00000245451.4 | P12644 | ||
| BMP4 | ENST00000558984.1 | TSL:1 | c.*148_*149insT | 3_prime_UTR | Exon 3 of 3 | ENSP00000454134.1 | P12644 | ||
| BMP4 | ENST00000559087.5 | TSL:1 | c.*148_*149insT | 3_prime_UTR | Exon 4 of 4 | ENSP00000453485.1 | P12644 |
Frequencies
GnomAD3 genomes 0.0155 AC: 2088AN: 134334Hom.: 19 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
2088
AN:
134334
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.115 AC: 58117AN: 503284Hom.: 387 Cov.: 0 AF XY: 0.114 AC XY: 29098AN XY: 254452 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
58117
AN:
503284
Hom.:
Cov.:
0
AF XY:
AC XY:
29098
AN XY:
254452
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
652
AN:
12332
American (AMR)
AF:
AC:
1033
AN:
14812
Ashkenazi Jewish (ASJ)
AF:
AC:
1201
AN:
12188
East Asian (EAS)
AF:
AC:
906
AN:
28642
South Asian (SAS)
AF:
AC:
2179
AN:
29148
European-Finnish (FIN)
AF:
AC:
3891
AN:
24384
Middle Eastern (MID)
AF:
AC:
144
AN:
1906
European-Non Finnish (NFE)
AF:
AC:
45280
AN:
353954
Other (OTH)
AF:
AC:
2831
AN:
25918
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.351
Heterozygous variant carriers
0
3441
6882
10324
13765
17206
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
946
1892
2838
3784
4730
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0155 AC: 2088AN: 134332Hom.: 19 Cov.: 0 AF XY: 0.0160 AC XY: 1036AN XY: 64668 show subpopulations
GnomAD4 genome
AF:
AC:
2088
AN:
134332
Hom.:
Cov.:
0
AF XY:
AC XY:
1036
AN XY:
64668
show subpopulations
African (AFR)
AF:
AC:
1076
AN:
33666
American (AMR)
AF:
AC:
153
AN:
13160
Ashkenazi Jewish (ASJ)
AF:
AC:
12
AN:
3268
East Asian (EAS)
AF:
AC:
11
AN:
4516
South Asian (SAS)
AF:
AC:
9
AN:
3532
European-Finnish (FIN)
AF:
AC:
173
AN:
8484
Middle Eastern (MID)
AF:
AC:
3
AN:
244
European-Non Finnish (NFE)
AF:
AC:
618
AN:
64710
Other (OTH)
AF:
AC:
20
AN:
1898
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
85
171
256
342
427
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
24
48
72
96
120
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
1
-
BMP4-Related Syndromic Microphthalmia (1)
-
1
-
Cleft Lip +/- Cleft Palate, Autosomal Dominant (1)
-
-
1
not provided (1)
-
1
-
Orofacial cleft (1)
-
1
-
Syndromic Microphthalmia, Dominant (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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