4-88182020-A-G

Variant names:

• chr4-88182020-A-G
• rs11724427
• ENST00000515655.5:c.-19-42006T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000515655.5(ABCG2):​c.-19-42006T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,058 control chromosomes in the GnomAD database, including 53,816 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 0.84 (53816 hom., cov: 30)
• Consequence: ABCG2 ENST00000515655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 2 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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_001348985.1	c.-20+29646T>C		intron_variant	Intron 2 of 16		NP_001335914.1
ABCG2	NM_001257386.2	c.-19-42006T>C		intron_variant	Intron 1 of 15		NP_001244315.1
ABCG2	XM_011532420.4	c.-20+28429T>C		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.-19-42006T>C		intron_variant	Intron 1 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.-20+29646T>C		intron_variant	Intron 2 of 16			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127619 AN: 151940 Hom.: 53762 Cov.: 30

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.861

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.849

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

GnomAD4 genome AF: 0.840 AC: 127732 AN: 152058 Hom.: 53816 Cov.: 30 AF XY: 0.841 AC XY: 62507 AN XY: 74320

African (AFR) AF: 0.878 AC: 36435 AN: 41502

American (AMR) AF: 0.845 AC: 12910 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.861 AC: 2984 AN: 3466

East Asian (EAS) AF: 0.997 AC: 5158 AN: 5174

South Asian (SAS) AF: 0.933 AC: 4498 AN: 4822

European-Finnish (FIN) AF: 0.777 AC: 8177 AN: 10526

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54719 AN: 67966

Other (OTH) AF: 0.851 AC: 1797 AN: 2112

Alfa AF: 0.835 Hom.: 12390

Bravo AF: 0.848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.68
DANN	Benign	0.46
PhyloP100		-2.1
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: rs11724427; hg19: chr4-89103172;