4-88129846-A-G

Variant names:

• chr4-88129846-A-G
• rs2725256
• NM_004827.3:c.531+1215T>C

Variant summary

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

The NM_004827.3(ABCG2):​c.531+1215T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,806 control chromosomes in the GnomAD database, including 9,756 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 0.36 (9756 hom., cov: 31)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.531+1215T>C		intron_variant	Intron 5 of 15	ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.531+1215T>C		intron_variant	Intron 5 of 15	1	NM_004827.3	ENSP00000237612.3
ABCG2	ENST00000515655.5	c.531+1215T>C		intron_variant	Intron 5 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.531+1215T>C		intron_variant	Intron 6 of 16			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54004 AN: 151690 Hom.: 9752 Cov.: 31

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.356 AC: 54030 AN: 151806 Hom.: 9756 Cov.: 31 AF XY: 0.351 AC XY: 26073 AN XY: 74188

African (AFR) AF: 0.334 AC: 13806 AN: 41368

American (AMR) AF: 0.332 AC: 5066 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1445 AN: 3466

East Asian (EAS) AF: 0.286 AC: 1474 AN: 5158

South Asian (SAS) AF: 0.381 AC: 1830 AN: 4804

European-Finnish (FIN) AF: 0.334 AC: 3525 AN: 10554

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25557 AN: 67880

Other (OTH) AF: 0.375 AC: 791 AN: 2112

Alfa AF: 0.369 Hom.: 45586

Bravo AF: 0.352

Asia WGS AF: 0.316 AC: 1102 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.60
PhyloP100		0.35
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: rs2725256; hg19: chr4-89050998;