NM_004827.3:c.421C>A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_004827.3(ABCG2):c.421C>A(p.Gln141Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,854 control chromosomes in the GnomAD database, including 12,079 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (★★★).
Frequency
Consequence
NM_004827.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCG2 | ENST00000237612.8 | c.421C>A | p.Gln141Lys | missense_variant | Exon 5 of 16 | 1 | NM_004827.3 | ENSP00000237612.3 | ||
ABCG2 | ENST00000515655.5 | c.421C>A | p.Gln141Lys | missense_variant | Exon 5 of 16 | 1 | ENSP00000426917.1 | |||
ABCG2 | ENST00000650821.1 | c.421C>A | p.Gln141Lys | missense_variant | Exon 6 of 17 | ENSP00000498246.1 |
Frequencies
GnomAD3 genomes AF: 0.0929 AC: 14129AN: 152046Hom.: 968 Cov.: 32
GnomAD3 exomes AF: 0.125 AC: 31308AN: 251158Hom.: 2764 AF XY: 0.118 AC XY: 16075AN XY: 135714
GnomAD4 exome AF: 0.114 AC: 166367AN: 1461690Hom.: 11106 Cov.: 31 AF XY: 0.112 AC XY: 81701AN XY: 727154
GnomAD4 genome AF: 0.0930 AC: 14145AN: 152164Hom.: 973 Cov.: 32 AF XY: 0.0930 AC XY: 6922AN XY: 74400
ClinVar
Submissions by phenotype
ABCG2-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Uric acid concentration, serum, quantitative trait locus 1 Other:1
- -
Gemcitabine response Other:1
- correlated with patient outcome with gemcitabine-based chemotherpy
rosuvastatin response - Metabolism/PK Other:1
PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Metabolism/PK
rosuvastatin response - Efficacy Other:1
PharmGKB Level of Evidence 2A: Variants in Level 2A clinical annotations are found in PharmGKB’s Tier 1 Very Important Pharmacogenes (VIPs). These variants are in known pharmacogenes, implying causation of drug phenotype is more likely. These clinical annotations describe variant-drug combinations with a moderate level of evidence supporting the association. For example, the association may be found in multiple cohorts, but there may be a minority of studies that do not support the majority assertion. Level 2A clinical annotations must be supported by at least two independent publications. Drug-variant association: Efficacy
BLOOD GROUP, JUNIOR SYSTEM Other:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at