rs3114020

Variant names:

• chr4-88162514-T-C
• rs3114020
• ENST00000515655.5:c.-19-22500A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-88162514-T-C
• chr4-88162514-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCG2	NM_001348985.1	c.-19-22500A>G		intron_variant	Intron 2 of 16		NP_001335914.1
ABCG2	NM_001257386.2	c.-19-22500A>G		intron_variant	Intron 1 of 15		NP_001244315.1
ABCG2	XM_011532420.4	c.-19-22500A>G		intron_variant	Intron 3 of 17		XP_011530722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000515655.5	c.-19-22500A>G		intron_variant	Intron 1 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.-19-22500A>G		intron_variant	Intron 2 of 16			ENSP00000498246.1

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

African (AFR) AF: 0.244 AC: 10131 AN: 41484

American (AMR) AF: 0.493 AC: 7513 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1669 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3427 AN: 5172

South Asian (SAS) AF: 0.458 AC: 2197 AN: 4798

European-Finnish (FIN) AF: 0.415 AC: 4371 AN: 10538

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31163 AN: 67932

Other (OTH) AF: 0.417 AC: 877 AN: 2102

Alfa AF: 0.446 Hom.: 60119

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
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3114020; hg19: chr4-89083666;