rs2725252

Positions:

• chr4-88140758-C-A
• chr4-88140758-C-T

Variant summary

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

The NM_004827.3(ABCG2):​c.-19-744G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,902 control chromosomes in the GnomAD database, including 16,867 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 0.46 (16867 hom., cov: 32)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.-19-744G>T		intron_variant		ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.-19-744G>T		intron_variant		1	NM_004827.3	ENSP00000237612.3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69941 AN: 151786 Hom.: 16870 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.460 AC: 69944 AN: 151902 Hom.: 16867 Cov.: 32 AF XY: 0.452 AC XY: 33564 AN XY: 74216

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.498

Alfa AF: 0.522 Hom.: 27597

Bravo AF: 0.449

Asia WGS AF: 0.414 AC: 1442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.37

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: rs2725252; hg19: chr4-89061910;