4-88174587-T-C

Variant names:

• chr4-88174587-T-C
• rs35229708
• ENST00000515655.5:c.-19-34573A>G

Variant summary

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

The ENST00000515655.5(ABCG2):​c.-19-34573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,040 control chromosomes in the GnomAD database, including 5,675 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 0.24 (5675 hom., cov: 32)
• Consequence: ABCG2 ENST00000515655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515655.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_001348985.1		c.-19-34573A>G		intron	N/A	NP_001335914.1
	ABCG2	NM_001257386.2		c.-19-34573A>G		intron	N/A	NP_001244315.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000515655.5	TSL:1	c.-19-34573A>G		intron	N/A	ENSP00000426917.1
	ABCG2	ENST00000650821.1		c.-19-34573A>G		intron	N/A	ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36069 AN: 151922 Hom.: 5664 Cov.: 32

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.237 AC: 36096 AN: 152040 Hom.: 5675 Cov.: 32 AF XY: 0.233 AC XY: 17312 AN XY: 74336

African (AFR) AF: 0.448 AC: 18533 AN: 41402

American (AMR) AF: 0.154 AC: 2351 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3472

East Asian (EAS) AF: 0.0776 AC: 402 AN: 5180

South Asian (SAS) AF: 0.199 AC: 958 AN: 4826

European-Finnish (FIN) AF: 0.135 AC: 1429 AN: 10580

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.161 AC: 10935 AN: 67990

Other (OTH) AF: 0.232 AC: 490 AN: 2110

Alfa AF: 0.215 Hom.: 585

Bravo AF: 0.247

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35229708; hg19: chr4-89095739;