8-66177084-G-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_000756.4(CRH):āc.394C>Gā(p.Leu132Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,445,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000756.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CRH | NM_000756.4 | c.394C>G | p.Leu132Val | missense_variant | 2/2 | ENST00000276571.5 | NP_000747.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CRH | ENST00000276571.5 | c.394C>G | p.Leu132Val | missense_variant | 2/2 | 1 | NM_000756.4 | ENSP00000276571 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000139 AC: 3AN: 215896Hom.: 0 AF XY: 0.00000850 AC XY: 1AN XY: 117628
GnomAD4 exome AF: 0.0000125 AC: 18AN: 1445654Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 10AN XY: 717868
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.394C>G (p.L132V) alteration is located in exon 2 (coding exon 1) of the CRH gene. This alteration results from a C to G substitution at nucleotide position 394, causing the leucine (L) at amino acid position 132 to be replaced by a valine (V). 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