NM_004827.3:c.1195-1469G>C

Variant names:

• chr4-88108735-C-G
• rs3114015
• NM_004827.3:c.1195-1469G>C

Variant summary

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

The NM_004827.3(ABCG2):​c.1195-1469G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,176 control chromosomes in the GnomAD database, including 56,100 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 0.85 (56100 hom., cov: 31)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.1195-1469G>C		intron_variant	Intron 9 of 15	ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.1195-1469G>C		intron_variant	Intron 9 of 15	1	NM_004827.3	ENSP00000237612.3
ABCG2	ENST00000515655.5	c.1195-1469G>C		intron_variant	Intron 9 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.1195-1469G>C		intron_variant	Intron 10 of 16			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128591 AN: 152058 Hom.: 56090 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.845 AC: 128653 AN: 152176 Hom.: 56100 Cov.: 31 AF XY: 0.844 AC XY: 62772 AN XY: 74390

African (AFR) AF: 0.627 AC: 25982 AN: 41444

American (AMR) AF: 0.802 AC: 12259 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3387 AN: 3472

East Asian (EAS) AF: 0.817 AC: 4229 AN: 5174

South Asian (SAS) AF: 0.874 AC: 4218 AN: 4826

European-Finnish (FIN) AF: 0.941 AC: 9979 AN: 10610

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.966 AC: 65702 AN: 68036

Other (OTH) AF: 0.859 AC: 1817 AN: 2116

Alfa AF: 0.900 Hom.: 3627

Bravo AF: 0.824

Asia WGS AF: 0.822 AC: 2862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.41
PhyloP100		0.25
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: rs3114015; hg19: chr4-89029887;