rs76945459
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002108.4(HAL):c.308+1G>A variant causes a splice donor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as association (★).
Frequency
Consequence
NM_002108.4 splice_donor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HAL | NM_002108.4 | c.308+1G>A | splice_donor_variant, intron_variant | Intron 3 of 20 | ENST00000261208.8 | NP_002099.1 | ||
HAL | NM_001258334.2 | c.308+1G>A | splice_donor_variant, intron_variant | Intron 3 of 19 | NP_001245263.1 | |||
HAL | NM_001258333.2 | c.-250+1G>A | splice_donor_variant, intron_variant | Intron 3 of 19 | NP_001245262.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251444Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460072Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726552
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74408
ClinVar
Submissions by phenotype
Increased histidine Other:1
Three heterozygous loss-of-function variants in HAL were found in 24/1152 African American individuals, in association with elevated serum histidine levels. Histidine level is a potential predictor of cardiovascular risk. Thus, loss-of-function variants in HAL may modify cardiovascular risk. Findings were replicated in a European American cohort. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at