rs3114020

chr4-88162514-T-Cchr4-88162514-T-G

Variant summary

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

The ENST00000515655.5(ABCG2):c.-19-22500A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,946 control chromosomes in the GnomAD database, including 13,706 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 0.41 (13706 hom., cov: 31)
• Consequence: ABCG2 ENST00000515655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG2	NM_001257386.2	c.-19-22500A>G		intron_variant
ABCG2	NM_001348985.1	c.-19-22500A>G		intron_variant
ABCG2	XM_011532420.4	c.-19-22500A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG2	ENST00000515655.5	c.-19-22500A>G		intron_variant		1
ABCG2	ENST00000650821.1	c.-19-22500A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61954 AN: 151830 Hom.: 13695 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.421

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.408 AC: 61987 AN: 151946 Hom.: 13706 Cov.: 31 AF XY: 0.408 AC XY: 30332 AN XY: 74280

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.481

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.417

Alfa AF: 0.449 Hom.: 26366

Bravo AF: 0.411

Asia WGS AF: 0.497 AC: 1718 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.2
Dann	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3114020; hg19: chr4-89083666;