rs4148152

chr4-88139757-T-C

Variant summary

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

The NM_004827.3(ABCG2):c.203+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 1,580,264 control chromosomes in the GnomAD database, including 6,031 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 0.076 (827 hom., cov: 33)
  • Exomes 𝑓: 0.059 (5204 hom.)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG2	NM_004827.3	c.203+36A>G		intron_variant		ENST00000237612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG2	ENST00000237612.8	c.203+36A>G		intron_variant		1	NM_004827.3	P1

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11494 AN: 152164 Hom.: 820 Cov.: 33

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0946

GnomAD3 exomes AF: 0.115 AC: 26001 AN: 226324 Hom.: 2510 AF XY: 0.110 AC XY: 13492 AN XY: 122572

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.328

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0404

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0595 AC: 84915 AN: 1427982 Hom.: 5204 Cov.: 28 AF XY: 0.0616 AC XY: 43725 AN XY: 709544

Gnomad4 AFR exome AF: 0.0516

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0342

Gnomad4 OTH exome AF: 0.0795

GnomAD4 genome AF: 0.0756 AC: 11519 AN: 152282 Hom.: 827 Cov.: 33 AF XY: 0.0840 AC XY: 6254 AN XY: 74460

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0374

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0533 Hom.: 385

Bravo AF: 0.0799

Asia WGS AF: 0.265 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.2
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4148152; hg19: chr4-89060909; COSMIC: COSV52942865;