rs45605536

Variant names:

• chr4-88097518-C-G
• NM_004827.3:c.1582G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-88097518-C-G
• chr4-88097518-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004827.3(ABCG2):​c.1582G>C​(p.Ala528Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A528T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCG2 NM_004827.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.1582G>C	p.Ala528Pro	missense_variant	Exon 13 of 16	ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.1582G>C	p.Ala528Pro	missense_variant	Exon 13 of 16	1	NM_004827.3	ENSP00000237612.3
ABCG2	ENST00000515655.5	c.1582G>C	p.Ala528Pro	missense_variant	Exon 13 of 16	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.1582G>C	p.Ala528Pro	missense_variant	Exon 14 of 17			ENSP00000498246.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	.;D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Uncertain	-0.019	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.097	T;D
Polyphen		0.99	D;B
Vest4		0.90
MutPred		0.75		Loss of glycosylation at S532 (P = 0.0934);Loss of glycosylation at S532 (P = 0.0934);
MVP		0.71
MPC		0.050
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-89018670;