NM_004827.3:c.1195-357T>C

Variant names:

• chr4-88107623-A-G
• rs2054576
• NM_004827.3:c.1195-357T>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.1195-357T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0806 in 152,294 control chromosomes in the GnomAD database, including 740 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 0.081 (740 hom., cov: 33)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 16 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.1195-357T>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.1195-357T>C		intron_variant	Intron 9 of 15	1	NM_004827.3	ENSP00000237612.3
ABCG2	ENST00000515655.5	c.1195-357T>C		intron_variant	Intron 9 of 15	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.1195-357T>C		intron_variant	Intron 10 of 16			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12254 AN: 152176 Hom.: 737 Cov.: 33

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.0689

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

GnomAD4 genome AF: 0.0806 AC: 12274 AN: 152294 Hom.: 740 Cov.: 33 AF XY: 0.0804 AC XY: 5989 AN XY: 74480

African (AFR) AF: 0.0284 AC: 1180 AN: 41572

American (AMR) AF: 0.131 AC: 2002 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1360 AN: 5180

South Asian (SAS) AF: 0.0675 AC: 326 AN: 4832

European-Finnish (FIN) AF: 0.0538 AC: 571 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6396 AN: 68004

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0901 Hom.: 1215

Bravo AF: 0.0873

Asia WGS AF: 0.150 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.16
DANN	Benign	0.55
PhyloP100		-1.4
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: rs2054576; hg19: chr4-89028775; COSMIC: COSV52949922;