chr4-88174538-G-A

Variant names:

• chr4-88174538-G-A
• rs55930652
• ENST00000515655.5:c.-19-34524C>T

Variant summary

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

The NM_001348985.1(ABCG2):​c.-19-34524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,976 control chromosomes in the GnomAD database, including 4,313 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 0.21 (4313 hom., cov: 32)
• Consequence: ABCG2 NM_001348985.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348985.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_001348985.1		c.-19-34524C>T		intron	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001257386.2		c.-19-34524C>T		intron	N/A	NP_001244315.1	Q9UNQ0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000515655.5	TSL:1	c.-19-34524C>T		intron	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000650821.1		c.-19-34524C>T		intron	N/A	ENSP00000498246.1	Q9UNQ0-1
	ABCG2	ENST00000889078.1		c.-19-34524C>T		intron	N/A	ENSP00000559137.1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32335 AN: 151858 Hom.: 4305 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.213 AC: 32350 AN: 151976 Hom.: 4313 Cov.: 32 AF XY: 0.214 AC XY: 15919 AN XY: 74280

African (AFR) AF: 0.0660 AC: 2738 AN: 41484

American (AMR) AF: 0.217 AC: 3307 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3466

East Asian (EAS) AF: 0.192 AC: 992 AN: 5156

South Asian (SAS) AF: 0.142 AC: 685 AN: 4818

European-Finnish (FIN) AF: 0.325 AC: 3428 AN: 10558

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20014 AN: 67910

Other (OTH) AF: 0.206 AC: 435 AN: 2108

Alfa AF: 0.246 Hom.: 627

Bravo AF: 0.199

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.60
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs55930652; hg19: chr4-89095690;