rs6857600

Variant names:

• chr4-88144923-C-T
• rs6857600
• NM_004827.3:c.-19-4909G>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.-19-4909G>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
• Publications: 13 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=-0.89).
• 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 rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.-19-4909G>A		intron_variant	Intron 1 of 15	ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.-19-4909G>A		intron_variant	Intron 1 of 15	1	NM_004827.3	ENSP00000237612.3

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

African (AFR) AF: 0.453 AC: 18705 AN: 41256

American (AMR) AF: 0.223 AC: 3402 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3466

East Asian (EAS) AF: 0.146 AC: 756 AN: 5164

South Asian (SAS) AF: 0.297 AC: 1425 AN: 4804

European-Finnish (FIN) AF: 0.238 AC: 2470 AN: 10396

Middle Eastern (MID) AF: 0.385 AC: 111 AN: 288

European-Non Finnish (NFE) AF: 0.195 AC: 13240 AN: 67858

Other (OTH) AF: 0.274 AC: 574 AN: 2092

Alfa AF: 0.225 Hom.: 16365

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
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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