rs754308298
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001202.6(BMP4):c.361C>T(p.His121Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H121R) has been classified as Likely benign.
Frequency
Consequence
NM_001202.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMP4 | NM_001202.6 | c.361C>T | p.His121Tyr | missense_variant | 3/4 | ENST00000245451.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMP4 | ENST00000245451.9 | c.361C>T | p.His121Tyr | missense_variant | 3/4 | 1 | NM_001202.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238904Hom.: 0 AF XY: 0.00000769 AC XY: 1AN XY: 130094
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1447256Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2AN XY: 720326
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Microphthalmia with brain and digit anomalies;C2677434:Orofacial cleft 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2017 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with BMP4-related disease. This variant is present in population databases (rs754308298, ExAC 0.002%). This sequence change replaces histidine with tyrosine at codon 121 of the BMP4 protein (p.His121Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at