4-88182020-A-C

Variant names:

• chr4-88182020-A-C
• rs11724427
• ENST00000515655.5:c.-19-42006T>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001348985.1(ABCG2):​c.-20+29646T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 152,102 control chromosomes in the GnomAD database, including 2 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 0.0011 (2 hom., cov: 30)
• Consequence: ABCG2 NM_001348985.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BS2: High Homozygotes in GnomAd4 at 2 BG gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_001348985.1	c.-20+29646T>G		intron_variant	Intron 2 of 16		NP_001335914.1
ABCG2	NM_001257386.2	c.-19-42006T>G		intron_variant	Intron 1 of 15		NP_001244315.1
ABCG2	XM_011532420.4	c.-20+28429T>G		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.-19-42006T>G		intron_variant	Intron 1 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.-20+29646T>G		intron_variant	Intron 2 of 16			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.00109 AC: 165 AN: 151984 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

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

GnomAD4 genome AF: 0.00109 AC: 166 AN: 152102 Hom.: 2 Cov.: 30 AF XY: 0.00130 AC XY: 97 AN XY: 74350

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00975

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11724427; hg19: chr4-89103172;