3-3179654-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The ENST00000231948.9(CRBN):āc.34C>Gā(p.His12Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,098 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H12P) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000231948.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRBN | NM_016302.4 | c.34C>G | p.His12Asp | missense_variant | 1/11 | ENST00000231948.9 | NP_057386.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRBN | ENST00000231948.9 | c.34C>G | p.His12Asp | missense_variant | 1/11 | 1 | NM_016302.4 | ENSP00000231948 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000809 AC: 2AN: 247290Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134508
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1460856Hom.: 1 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 726796
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 02, 2022 | The c.34C>G (p.H12D) alteration is located in exon 1 (coding exon 1) of the CRBN gene. This alteration results from a C to G substitution at nucleotide position 34, causing the histidine (H) at amino acid position 12 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at