rs6857600

Positions:

• chr4-88144923-C-T

Variant summary

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

The NM_004827.3(ABCG2):​c.-19-4909G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,462 control chromosomes in the GnomAD database, including 6,756 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 0.28 (6756 hom., cov: 31)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG2	NM_004827.3	c.-19-4909G>A		intron_variant		ENST00000237612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG2	ENST00000237612.8	c.-19-4909G>A		intron_variant		1	NM_004827.3	P1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41816 AN: 151342 Hom.: 6753 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.390

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.276 AC: 41837 AN: 151462 Hom.: 6756 Cov.: 31 AF XY: 0.275 AC XY: 20358 AN XY: 73960

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.274

Alfa AF: 0.217 Hom.: 6436

Bravo AF: 0.282

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.67
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs6857600; hg19: chr4-89066075; COSMIC: COSV52947248;