4-88118106-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate
The NM_004827.3(ABCG2):c.841+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,612,120 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000085 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 3 hom. )
Consequence
ABCG2
NM_004827.3 splice_donor_region, intron
NM_004827.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9936
2
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
ABCG2 (HGNC:74): (ATP binding cassette subfamily G member 2 (JR blood group)) The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
BP6
?
Variant 4-88118106-T-C is Benign according to our data. Variant chr4-88118106-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3057392.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCG2 | NM_004827.3 | c.841+3A>G | splice_donor_region_variant, intron_variant | ENST00000237612.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCG2 | ENST00000237612.8 | c.841+3A>G | splice_donor_region_variant, intron_variant | 1 | NM_004827.3 | P1 | |||
ABCG2 | ENST00000515655.5 | c.841+3A>G | splice_donor_region_variant, intron_variant | 1 | |||||
ABCG2 | ENST00000650821.1 | c.841+3A>G | splice_donor_region_variant, intron_variant | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152126Hom.: 1 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
13
AN:
152126
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000301 AC: 75AN: 248958Hom.: 1 AF XY: 0.000439 AC XY: 59AN XY: 134478
GnomAD3 exomes
AF:
AC:
75
AN:
248958
Hom.:
AF XY:
AC XY:
59
AN XY:
134478
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000149 AC: 217AN: 1459876Hom.: 3 Cov.: 30 AF XY: 0.000207 AC XY: 150AN XY: 726100
GnomAD4 exome
AF:
AC:
217
AN:
1459876
Hom.:
Cov.:
30
AF XY:
AC XY:
150
AN XY:
726100
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152244Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74444
GnomAD4 genome
?
AF:
AC:
13
AN:
152244
Hom.:
Cov.:
32
AF XY:
AC XY:
13
AN XY:
74444
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
6
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ABCG2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 12, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at