4-88139757-T-C

Variant names:

• chr4-88139757-T-C
• rs4148152
• NM_004827.3:c.203+36A>G

Variant summary

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

The NM_004827.3(ABCG2):​c.203+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 1,580,264 control chromosomes in the GnomAD database, including 6,031 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 0.076 (827 hom., cov: 33)
  • Exomes 𝑓: 0.059 (5204 hom.)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 21 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 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.203+36A>G		intron	N/A	NP_004818.2	Q9UNQ0-1
	ABCG2	NM_001348985.1		c.203+36A>G		intron	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001348986.2		c.203+36A>G		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.203+36A>G		intron	N/A	ENSP00000237612.3	Q9UNQ0-1
	ABCG2	ENST00000515655.5	TSL:1	c.203+36A>G		intron	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000503830.2	TSL:1	c.203+36A>G		intron	N/A	ENSP00000426934.2	F8S0F2

Frequencies

GnomAD3 genomes AF: 0.0755 AC: 11494 AN: 152164 Hom.: 820 Cov.: 33

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0946

GnomAD2 exomes AF: 0.115 AC: 26001 AN: 226324 AF XY: 0.110

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.328

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0404

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0595 AC: 84915 AN: 1427982 Hom.: 5204 Cov.: 28 AF XY: 0.0616 AC XY: 43725 AN XY: 709544

African (AFR) AF: 0.0516 AC: 1677 AN: 32472

American (AMR) AF: 0.227 AC: 9536 AN: 41950

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 2625 AN: 25188

East Asian (EAS) AF: 0.266 AC: 10392 AN: 39136

South Asian (SAS) AF: 0.141 AC: 11645 AN: 82830

European-Finnish (FIN) AF: 0.124 AC: 6502 AN: 52554

Middle Eastern (MID) AF: 0.101 AC: 577 AN: 5686

European-Non Finnish (NFE) AF: 0.0342 AC: 37267 AN: 1089088

Other (OTH) AF: 0.0795 AC: 4694 AN: 59078

GnomAD4 genome AF: 0.0756 AC: 11519 AN: 152282 Hom.: 827 Cov.: 33 AF XY: 0.0840 AC XY: 6254 AN XY: 74460

African (AFR) AF: 0.0527 AC: 2192 AN: 41556

American (AMR) AF: 0.155 AC: 2374 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1633 AN: 5178

South Asian (SAS) AF: 0.159 AC: 767 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1355 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0374 AC: 2541 AN: 68028

Other (OTH) AF: 0.104 AC: 219 AN: 2114

Alfa AF: 0.0532 Hom.: 1051

Bravo AF: 0.0799

Asia WGS AF: 0.265 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.63
PhyloP100		-0.52
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: rs4148152; hg19: chr4-89060909; COSMIC: COSV52942865;