NM_004827.3:c.1368-334C>T

Variant names:

• chr4-88099782-G-A
• rs4148157
• NM_004827.3:c.1368-334C>T

Variant summary

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

The NM_004827.3(ABCG2):​c.1368-334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 152,102 control chromosomes in the GnomAD database, including 734 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 (734 hom., cov: 31)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 29 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004827.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_004827.3	MANE Select	c.1368-334C>T		intron	N/A	NP_004818.2	Q9UNQ0-1
	ABCG2	NM_001348985.1		c.1368-334C>T		intron	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001348986.2		c.1368-334C>T		intron	N/A	NP_001335915.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.1368-334C>T		intron	N/A	ENSP00000237612.3	Q9UNQ0-1
	ABCG2	ENST00000515655.5	TSL:1	c.1368-334C>T		intron	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000889086.1		c.1455-334C>T		intron	N/A	ENSP00000559145.1

Frequencies

GnomAD3 genomes AF: 0.0806 AC: 12252 AN: 151984 Hom.: 731 Cov.: 31

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0690

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

GnomAD4 genome AF: 0.0807 AC: 12275 AN: 152102 Hom.: 734 Cov.: 31 AF XY: 0.0802 AC XY: 5965 AN XY: 74362

African (AFR) AF: 0.0297 AC: 1234 AN: 41500

American (AMR) AF: 0.131 AC: 1999 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3468

East Asian (EAS) AF: 0.262 AC: 1351 AN: 5166

South Asian (SAS) AF: 0.0646 AC: 311 AN: 4812

European-Finnish (FIN) AF: 0.0539 AC: 570 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0937 AC: 6372 AN: 67982

Other (OTH) AF: 0.0707 AC: 149 AN: 2108

Alfa AF: 0.0874 Hom.: 1618

Bravo AF: 0.0875

Asia WGS AF: 0.148 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.082
DANN	Benign	0.60
PhyloP100		-1.7
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: rs4148157; hg19: chr4-89020934;