chr18-24477510-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_021624.4(HRH4):c.1121G>T(p.Cys374Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,605,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021624.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRH4 | NM_021624.4 | c.1121G>T | p.Cys374Phe | missense_variant | 3/3 | ENST00000256906.5 | |
HRH4 | NM_001143828.2 | c.857G>T | p.Cys286Phe | missense_variant | 2/2 | ||
HRH4 | NM_001160166.2 | c.*753G>T | 3_prime_UTR_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRH4 | ENST00000256906.5 | c.1121G>T | p.Cys374Phe | missense_variant | 3/3 | 1 | NM_021624.4 | P1 | |
HRH4 | ENST00000426880.2 | c.857G>T | p.Cys286Phe | missense_variant | 2/2 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152062Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000204 AC: 5AN: 245440Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133012
GnomAD4 exome AF: 0.0000186 AC: 27AN: 1453202Hom.: 0 Cov.: 32 AF XY: 0.0000222 AC XY: 16AN XY: 722340
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152062Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | The c.1121G>T (p.C374F) alteration is located in exon 3 (coding exon 3) of the HRH4 gene. This alteration results from a G to T substitution at nucleotide position 1121, causing the cysteine (C) at amino acid position 374 to be replaced by a phenylalanine (F). 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