ENST00000505480.6:c.-285T>C

Variant names:

• chr4-88158842-A-G
• rs2231135
• ENST00000505480.6:c.-285T>C

Variant summary

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

The ENST00000505480.6(ABCG2):​c.-285T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 334,338 control chromosomes in the GnomAD database, including 625 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 0.048 (229 hom., cov: 33)
  • Exomes 𝑓: 0.061 (396 hom.)
• Consequence: ABCG2 ENST00000505480.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 9 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000505480.6. 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_001348986.2		c.-285T>C		5_prime_UTR	Exon 1 of 16	NP_001335915.1
	ABCG2	NM_001348988.1		c.-670T>C		5_prime_UTR	Exon 1 of 17	NP_001335917.1	Q9UNQ0-1
	ABCG2	NM_001348987.1		c.-476T>C		5_prime_UTR	Exon 1 of 16	NP_001335916.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000505480.6	TSL:1	c.-285T>C		5_prime_UTR	Exon 1 of 4	ENSP00000426916.2	F8S0F2
	ABCG2	ENST00000515655.5	TSL:1	c.-19-18828T>C		intron	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000503830.2	TSL:1	c.-20+363T>C		intron	N/A	ENSP00000426934.2	F8S0F2

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7240 AN: 152090 Hom.: 228 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0497

GnomAD4 exome AF: 0.0615 AC: 11196 AN: 182134 Hom.: 396 Cov.: 0 AF XY: 0.0623 AC XY: 6460 AN XY: 103770

African (AFR) AF: 0.0157 AC: 21 AN: 1340

American (AMR) AF: 0.0493 AC: 337 AN: 6840

Ashkenazi Jewish (ASJ) AF: 0.0549 AC: 184 AN: 3352

East Asian (EAS) AF: 0.000221 AC: 1 AN: 4520

South Asian (SAS) AF: 0.0624 AC: 2555 AN: 40936

European-Finnish (FIN) AF: 0.0711 AC: 621 AN: 8734

Middle Eastern (MID) AF: 0.0570 AC: 34 AN: 596

European-Non Finnish (NFE) AF: 0.0650 AC: 6966 AN: 107208

Other (OTH) AF: 0.0554 AC: 477 AN: 8608

GnomAD4 genome AF: 0.0476 AC: 7239 AN: 152204 Hom.: 229 Cov.: 33 AF XY: 0.0486 AC XY: 3618 AN XY: 74416

African (AFR) AF: 0.0183 AC: 761 AN: 41558

American (AMR) AF: 0.0514 AC: 786 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.0566 AC: 273 AN: 4820

European-Finnish (FIN) AF: 0.0693 AC: 735 AN: 10608

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0631 AC: 4292 AN: 67982

Other (OTH) AF: 0.0492 AC: 104 AN: 2114

Alfa AF: 0.0550 Hom.: 105

Bravo AF: 0.0438

Asia WGS AF: 0.0260 AC: 91 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.6
DANN	Benign	0.65
PhyloP100		0.095
PromoterAI		0.044	Neutral
Mutation Taster		=300/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2231135;

hg19: chr4-89079994;