4-88175999-C-A

Variant names:

• chr4-88175999-C-A
• rs1481014
• ENST00000515655.5:c.-19-35985G>T

Variant summary

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

The ENST00000515655.5(ABCG2):​c.-19-35985G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,098 control chromosomes in the GnomAD database, including 5,714 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 (5714 hom., cov: 33)
• Consequence: ABCG2 ENST00000515655.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_001348985.1	c.-20+35667G>T		intron_variant	Intron 2 of 16		NP_001335914.1
ABCG2	NM_001257386.2	c.-19-35985G>T		intron_variant	Intron 1 of 15		NP_001244315.1
ABCG2	XM_011532420.4	c.-20+34450G>T		intron_variant	Intron 3 of 17		XP_011530722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000515655.5	c.-19-35985G>T		intron_variant	Intron 1 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.-20+35667G>T		intron_variant	Intron 2 of 16			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36226 AN: 151980 Hom.: 5701 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.320

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: 0.238 AC: 36256 AN: 152098 Hom.: 5714 Cov.: 33 AF XY: 0.234 AC XY: 17402 AN XY: 74374

African (AFR) AF: 0.450 AC: 18658 AN: 41432

American (AMR) AF: 0.155 AC: 2367 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3470

East Asian (EAS) AF: 0.0775 AC: 402 AN: 5188

South Asian (SAS) AF: 0.198 AC: 956 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10596

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10948 AN: 67994

Other (OTH) AF: 0.232 AC: 491 AN: 2112

Alfa AF: 0.185 Hom.: 1667

Bravo AF: 0.248

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.41
DANN	Benign	0.48
PhyloP100		-0.91
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: rs1481014; hg19: chr4-89097151;