NM_004827.3:c.-19-8240A>G

Variant names:

• chr4-88148254-T-C
• rs2622624
• NM_004827.3:c.-19-8240A>G

Variant summary

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

The NM_004827.3(ABCG2):​c.-19-8240A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 151,926 control chromosomes in the GnomAD database, including 13,846 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 (13846 hom., cov: 31)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 13 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.-19-8240A>G		intron_variant	Intron 1 of 15	ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.-19-8240A>G		intron_variant	Intron 1 of 15	1	NM_004827.3	ENSP00000237612.3

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62472 AN: 151808 Hom.: 13834 Cov.: 31

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.411 AC: 62511 AN: 151926 Hom.: 13846 Cov.: 31 AF XY: 0.410 AC XY: 30433 AN XY: 74234

African (AFR) AF: 0.258 AC: 10696 AN: 41378

American (AMR) AF: 0.492 AC: 7517 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1712 AN: 3472

East Asian (EAS) AF: 0.666 AC: 3447 AN: 5172

South Asian (SAS) AF: 0.451 AC: 2166 AN: 4806

European-Finnish (FIN) AF: 0.382 AC: 4030 AN: 10558

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31396 AN: 67960

Other (OTH) AF: 0.426 AC: 898 AN: 2110

Alfa AF: 0.437 Hom.: 21449

Bravo AF: 0.418

Asia WGS AF: 0.497 AC: 1726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	7.8
DANN	Benign	0.66
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2622624; hg19: chr4-89069406;