rs2231153

Variant names:

• chr4-88101210-C-T
• rs2231153
• NM_004827.3:c.1367+20G>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.1367+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 1,612,036 control chromosomes in the GnomAD database, including 687,373 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 0.76 (49053 hom., cov: 31)
  • Exomes 𝑓: 0.93 (638320 hom.)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.954 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_004827.3	MANE Select	c.1367+20G>A		intron	N/A	NP_004818.2	Q9UNQ0-1
	ABCG2	NM_001348985.1		c.1367+20G>A		intron	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001348986.2		c.1367+20G>A		intron	N/A	NP_001335915.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.1367+20G>A		intron	N/A	ENSP00000237612.3	Q9UNQ0-1
	ABCG2	ENST00000515655.5	TSL:1	c.1367+20G>A		intron	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000889086.1		c.1454+20G>A		intron	N/A	ENSP00000559145.1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115341 AN: 151936 Hom.: 49048 Cov.: 31

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.783

GnomAD2 exomes AF: 0.859 AC: 215560 AN: 250952 AF XY: 0.875

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.951

Gnomad EAS exome AF: 0.783

Gnomad FIN exome AF: 0.940

Gnomad NFE exome AF: 0.960

Gnomad OTH exome AF: 0.892

GnomAD4 exome AF: 0.928 AC: 1355561 AN: 1459982 Hom.: 638320 Cov.: 32 AF XY: 0.929 AC XY: 674833 AN XY: 726498

African (AFR) AF: 0.320 AC: 10710 AN: 33424

American (AMR) AF: 0.737 AC: 32939 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 24809 AN: 26120

East Asian (EAS) AF: 0.801 AC: 31797 AN: 39678

South Asian (SAS) AF: 0.860 AC: 74135 AN: 86172

European-Finnish (FIN) AF: 0.945 AC: 50466 AN: 53408

Middle Eastern (MID) AF: 0.871 AC: 5022 AN: 5764

European-Non Finnish (NFE) AF: 0.965 AC: 1071795 AN: 1110426

Other (OTH) AF: 0.893 AC: 53888 AN: 60314

GnomAD4 genome AF: 0.759 AC: 115379 AN: 152054 Hom.: 49053 Cov.: 31 AF XY: 0.760 AC XY: 56474 AN XY: 74334

African (AFR) AF: 0.348 AC: 14411 AN: 41412

American (AMR) AF: 0.758 AC: 11579 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3280 AN: 3470

East Asian (EAS) AF: 0.794 AC: 4109 AN: 5176

South Asian (SAS) AF: 0.840 AC: 4045 AN: 4814

European-Finnish (FIN) AF: 0.940 AC: 9944 AN: 10576

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.960 AC: 65323 AN: 68018

Other (OTH) AF: 0.781 AC: 1650 AN: 2112

Alfa AF: 0.882 Hom.: 184395

Bravo AF: 0.725

Asia WGS AF: 0.773 AC: 2690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2231153; hg19: chr4-89022362; COSMIC: COSV52945549;