rs2231153

chr4-88101210-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004827.3(ABCG2):c.1367+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 1,612,036 control chromosomes in the GnomAD database, including 687,373 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (49053 hom., cov: 31)
  • Exomes 𝑓: 0.93 (638320 hom.)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG2	NM_004827.3	c.1367+20G>A		intron_variant		ENST00000237612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG2	ENST00000237612.8	c.1367+20G>A		intron_variant		1	NM_004827.3	P1
ABCG2	ENST00000515655.5	c.1367+20G>A		intron_variant		1
ABCG2	ENST00000650821.1	c.1367+20G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115341 AN: 151936 Hom.: 49048 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.783

GnomAD3 exomes AF: 0.859 AC: 215560 AN: 250952 Hom.: 96027 AF XY: 0.875 AC XY: 118714 AN XY: 135648

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.951

Gnomad EAS exome AF: 0.783

Gnomad SAS exome AF: 0.857

Gnomad FIN exome AF: 0.940

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.892

GnomAD4 exome AF: 0.928 AC: 1355561 AN: 1459982 Hom.: 638320 Cov.: 32 AF XY: 0.929 AC XY: 674833 AN XY: 726498

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.737

Gnomad4 ASJ exome AF: 0.950

Gnomad4 EAS exome AF: 0.801

Gnomad4 SAS exome AF: 0.860

Gnomad4 FIN exome AF: 0.945

Gnomad4 NFE exome AF: 0.965

Gnomad4 OTH exome AF: 0.893

GnomAD4 genome AF: 0.759 AC: 115379 AN: 152054 Hom.: 49053 Cov.: 31 AF XY: 0.760 AC XY: 56474 AN XY: 74334

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.945

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.960

Gnomad4 OTH AF: 0.781

Alfa AF: 0.910 Hom.: 85253

Bravo AF: 0.725

Asia WGS AF: 0.773 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.0
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2231153; hg19: chr4-89022362; COSMIC: COSV52945549;