rs2725252

Variant names:

• chr4-88140758-C-A
• rs2725252
• NM_004827.3:c.-19-744G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_004827.3(ABCG2):​c.-19-744G>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
• Publications: 17 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=-0.87).
• 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 rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.-19-744G>T		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.-19-744G>T		intron_variant	Intron 1 of 15	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

African (AFR) AF: 0.314 AC: 12994 AN: 41418

American (AMR) AF: 0.443 AC: 6756 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2100 AN: 3466

East Asian (EAS) AF: 0.406 AC: 2094 AN: 5156

South Asian (SAS) AF: 0.476 AC: 2293 AN: 4822

European-Finnish (FIN) AF: 0.457 AC: 4806 AN: 10518

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37175 AN: 67954

Other (OTH) AF: 0.498 AC: 1049 AN: 2108

Alfa AF: 0.513 Hom.: 61142

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
PhyloP100		0.23
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: rs2725252; hg19: chr4-89061910;