chr12-27390208-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_020183.6(BMAL2):c.888G>C(p.Glu296Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,613,892 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0079 ( 16 hom., cov: 32)
Exomes 𝑓: 0.00081 ( 31 hom. )
Consequence
BMAL2
NM_020183.6 missense
NM_020183.6 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: -0.0700
Genes affected
BMAL2 (HGNC:18984): (basic helix-loop-helix ARNT like 2) This gene encodes a basic helix-loop-helix transcription factor belonging to the PAS (PER, ARNT, SIM) superfamily. The PAS proteins play important roles in adaptation to low atmospheric and cellular oxygen levels, exposure to certain environmental pollutants, and diurnal oscillations in light and temperature. This protein forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha. Consistent with its role as a biologically relevant partner of circadian and hypoxia factors, this protein is coexpressed in regions of the brain such as the thalamus, hypothalamus, and amygdala. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0043046772).
BP6
?
Variant 12-27390208-G-C is Benign according to our data. Variant chr12-27390208-G-C is described in ClinVar as [Benign]. Clinvar id is 789045.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00786 (1196/152256) while in subpopulation AFR AF= 0.0271 (1126/41540). AF 95% confidence interval is 0.0258. There are 16 homozygotes in gnomad4. There are 542 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 16 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BMAL2 | NM_020183.6 | c.888G>C | p.Glu296Asp | missense_variant | 9/17 | ENST00000266503.10 | |
BMAL2-AS1 | NR_109975.1 | n.434-40C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BMAL2 | ENST00000266503.10 | c.888G>C | p.Glu296Asp | missense_variant | 9/17 | 1 | NM_020183.6 | P2 | |
BMAL2-AS1 | ENST00000500498.2 | n.425-40C>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00785 AC: 1195AN: 152138Hom.: 16 Cov.: 32
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GnomAD3 exomes AF: 0.00218 AC: 548AN: 251226Hom.: 6 AF XY: 0.00147 AC XY: 199AN XY: 135756
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GnomAD4 exome AF: 0.000813 AC: 1189AN: 1461636Hom.: 31 Cov.: 30 AF XY: 0.000682 AC XY: 496AN XY: 727144
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GnomAD4 genome ? AF: 0.00786 AC: 1196AN: 152256Hom.: 16 Cov.: 32 AF XY: 0.00728 AC XY: 542AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 24, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
D;P;.;B;P;B;.
Vest4
MutPred
0.40
.;.;.;.;.;Gain of catalytic residue at E296 (P = 0);.;
MVP
MPC
0.51
ClinPred
T
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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