4-88147303-G-T

Variant names:

• chr4-88147303-G-T
• rs17731799
• NM_004827.3:c.-19-7289C>A

Variant summary

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

The NM_004827.3(ABCG2):​c.-19-7289C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,832 control chromosomes in the GnomAD database, including 14,603 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 0.43 (14603 hom., cov: 31)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.935
• Publications: 15 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004827.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_004827.3	MANE Select	c.-19-7289C>A		intron	N/A	NP_004818.2
	ABCG2	NM_001348985.1		c.-19-7289C>A		intron	N/A	NP_001335914.1
	ABCG2	NM_001348986.2		c.-19-7289C>A		intron	N/A	NP_001335915.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.-19-7289C>A		intron	N/A	ENSP00000237612.3
	ABCG2	ENST00000515655.5	TSL:1	c.-19-7289C>A		intron	N/A	ENSP00000426917.1
	ABCG2	ENST00000503830.2	TSL:1	c.-19-7289C>A		intron	N/A	ENSP00000426934.2

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64974 AN: 151714 Hom.: 14588 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.428 AC: 65025 AN: 151832 Hom.: 14603 Cov.: 31 AF XY: 0.427 AC XY: 31642 AN XY: 74174

African (AFR) AF: 0.316 AC: 13076 AN: 41414

American (AMR) AF: 0.497 AC: 7588 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1708 AN: 3464

East Asian (EAS) AF: 0.667 AC: 3424 AN: 5130

South Asian (SAS) AF: 0.470 AC: 2263 AN: 4810

European-Finnish (FIN) AF: 0.384 AC: 4033 AN: 10516

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31363 AN: 67932

Other (OTH) AF: 0.436 AC: 919 AN: 2106

Alfa AF: 0.408 Hom.: 7669

Bravo AF: 0.436

Asia WGS AF: 0.519 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.81
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17731799; hg19: chr4-89068455;