dbSNP rs1481014: ABCG2:c.-19-35985G>T (chr4-88175999-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348985.1(ABCG2):c.-20+35667G>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
NM_001348985.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.906

Publications

9 publications found

Variant links:

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]

ABCG2 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348985.1. 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_001348985.1		c.-20+35667G>T		intron	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001257386.2		c.-19-35985G>T		intron	N/A	NP_001244315.1	Q9UNQ0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCG2	ENST00000515655.5	TSL:1	c.-19-35985G>T	intron	N/A	ENSP00000426917.1	Q9UNQ0-2
ABCG2	ENST00000650821.1		c.-20+35667G>T	intron	N/A	ENSP00000498246.1	Q9UNQ0-1
ABCG2	ENST00000889078.1		c.-19-35985G>T	intron	N/A	ENSP00000559137.1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36226

AN:

151980

Hom.:

5701

Cov.:

show subpopulations

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.:

AF XY:

0.234

AC XY:

17402

AN XY:

74374

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10948

AN:

67994

Other (OTH)

AF:

0.232

AC:

491

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1276

2551

3827

5102

6378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.41

(source)

DANN

Benign

0.48

PhyloP100

-0.91

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over