chr4-88143450-C-T

Variant names:

• chr4-88143450-C-T
• rs3109823
• NM_004827.3:c.-19-3436G>A

Variant summary

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

The NM_004827.3(ABCG2):​c.-19-3436G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,964 control chromosomes in the GnomAD database, including 33,945 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 0.65 (33945 hom., cov: 32)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.782

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.-19-3436G>A		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.-19-3436G>A		intron_variant	Intron 1 of 15	1	NM_004827.3	ENSP00000237612.3

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99366 AN: 151844 Hom.: 33930 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.654 AC: 99415 AN: 151964 Hom.: 33945 Cov.: 32 AF XY: 0.656 AC XY: 48751 AN XY: 74302

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.706

Alfa AF: 0.714 Hom.: 38838

Bravo AF: 0.648

Asia WGS AF: 0.742 AC: 2580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.9
DANN	Benign	0.83

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: rs3109823; hg19: chr4-89064602;