rs55930652

Positions:

• chr4-88174538-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000515655.5(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 ENST00000515655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG2	NM_001257386.2	c.-19-34524C>T		intron_variant			NP_001244315.1
ABCG2	NM_001348985.1	c.-19-34524C>T		intron_variant			NP_001335914.1
ABCG2	XM_011532420.4	c.-19-34524C>T		intron_variant			XP_011530722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000515655.5	c.-19-34524C>T		intron_variant		1		ENSP00000426917
ABCG2	ENST00000650821.1	c.-19-34524C>T		intron_variant				ENSP00000498246	P1

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

Gnomad4 AFR AF: 0.0660

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.206

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55930652; hg19: chr4-89095690;