19-40447951-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000713.3(BLVRB):c.559C>T(p.Arg187Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
BLVRB
NM_000713.3 missense
NM_000713.3 missense
Scores
3
10
Clinical Significance
Conservation
PhyloP100: 0.963
Genes affected
BLVRB (HGNC:1063): (biliverdin reductase B) Enables biliverdin reductase (NAD(P)+) activity and riboflavin reductase (NADPH) activity. Involved in heme catabolic process. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36570063).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLVRB | NM_000713.3 | c.559C>T | p.Arg187Cys | missense_variant | 5/5 | ENST00000263368.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLVRB | ENST00000263368.9 | c.559C>T | p.Arg187Cys | missense_variant | 5/5 | 1 | NM_000713.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152106Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251452Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461876Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727244
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152106Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74296
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 23, 2022 | The c.559C>T (p.R187C) alteration is located in exon 5 (coding exon 5) of the BLVRB gene. This alteration results from a C to T substitution at nucleotide position 559, causing the arginine (R) at amino acid position 187 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
0.97
.;.;D
Vest4
0.29, 0.27
MutPred
0.57
.;.;Gain of sheet (P = 0.0011);
MVP
0.57
MPC
0.65
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at