4-88158234-T-C

Variant names:

• chr4-88158234-T-C
• rs2622605
• NM_004827.3:c.-20+152A>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.-20+152A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,086 control chromosomes in the GnomAD database, including 13,674 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 0.41 (13674 hom., cov: 32)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 12 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]

LOC124900867 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 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.-20+152A>G		intron	N/A	NP_004818.2	Q9UNQ0-1
	ABCG2	NM_001348985.1		c.-19-18220A>G		intron	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001348986.2		c.-20+343A>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.-20+152A>G		intron	N/A	ENSP00000237612.3	Q9UNQ0-1
	ABCG2	ENST00000515655.5	TSL:1	c.-19-18220A>G		intron	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000503830.2	TSL:1	c.-20+971A>G		intron	N/A	ENSP00000426934.2	F8S0F2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61927 AN: 151968 Hom.: 13661 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.407 AC: 61964 AN: 152086 Hom.: 13674 Cov.: 32 AF XY: 0.407 AC XY: 30283 AN XY: 74340

African (AFR) AF: 0.244 AC: 10116 AN: 41498

American (AMR) AF: 0.493 AC: 7530 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1669 AN: 3468

East Asian (EAS) AF: 0.663 AC: 3423 AN: 5164

South Asian (SAS) AF: 0.449 AC: 2163 AN: 4820

European-Finnish (FIN) AF: 0.413 AC: 4369 AN: 10566

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.459 AC: 31172 AN: 67966

Other (OTH) AF: 0.417 AC: 881 AN: 2112

Alfa AF: 0.447 Hom.: 25995

Bravo AF: 0.411

Asia WGS AF: 0.494 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.50
PhyloP100		2.0
PromoterAI		-0.0062	Neutral
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: rs2622605; hg19: chr4-89079386;