rs2231137

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004827.3(ABCG2):c.34G>A(p.Val12Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,613,912 control chromosomes in the GnomAD database, including 6,281 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,Affects,association (no stars).

Frequency

Genomes: 𝑓 0.078 ( 846 hom., cov: 33)

Exomes 𝑓: 0.060 ( 5435 hom. )

Consequence

ABCG2
NM_004827.3 missense

Scores

Clinical Significance

Likely benign; Affects; association no assertion criteria provided B:1O:2

Conservation

PhyloP100: 0.210

Publications

308 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050233305).

BP6

Variant 4-88139962-C-T is Benign according to our data. Variant chr4-88139962-C-T is described in ClinVar as Likely_benign|Affects|association. ClinVar VariationId is 30386.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3 link	c.34G>A	p.Val12Met	missense_variant	Exon 2 of 16	ENST00000237612.8	NP_004818.2	Q9UNQ0-1A1LUE4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8 link	c.34G>A	p.Val12Met	missense_variant	Exon 2 of 16	1	NM_004827.3	ENSP00000237612.3		Q9UNQ0-1

Frequencies

GnomAD3 genomes

AF:

0.0782

AC:

11894

AN:

152128

Hom.:

837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.313

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0979

GnomAD2 exomes

AF:

0.114

AC:

28639

AN:

250804

AF XY:

0.109

show subpopulations

Gnomad AFR exome

AF:

0.0660

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.326

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.0408

Gnomad OTH exome

AF:

0.104

GnomAD4 exome

AF:

0.0598

AC:

87391

AN:

1461666

Hom.:

5435

Cov.:

AF XY:

0.0618

AC XY:

44971

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.0638

AC:

2135

AN:

33476

American (AMR)

AF:

0.229

AC:

10228

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2744

AN:

26126

East Asian (EAS)

AF:

0.265

AC:

10536

AN:

39694

South Asian (SAS)

AF:

0.140

AC:

12048

AN:

86234

European-Finnish (FIN)

AF:

0.124

AC:

6594

AN:

53370

Middle Eastern (MID)

AF:

0.102

AC:

588

AN:

5768

European-Non Finnish (NFE)

AF:

0.0339

AC:

37733

AN:

1111930

Other (OTH)

AF:

0.0792

AC:

4785

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

4125

8249

12374

16498

20623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1754

3508

5262

7016

8770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0783

AC:

11926

AN:

152246

Hom.:

846

Cov.:

AF XY:

0.0867

AC XY:

6452

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0638

AC:

2650

AN:

41536

American (AMR)

AF:

0.156

AC:

2382

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

355

AN:

3472

East Asian (EAS)

AF:

0.312

AC:

1616

AN:

5176

South Asian (SAS)

AF:

0.157

AC:

757

AN:

4822

European-Finnish (FIN)

AF:

0.128

AC:

1354

AN:

10596

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0371

AC:

2523

AN:

68034

Other (OTH)

AF:

0.107

AC:

226

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

520

1041

1561

2082

2602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<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:

0.0588

Hom.:

1164

Bravo

AF:

0.0829

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0340

AC:

131

ESP6500AA

AF:

0.0606

AC:

267

ESP6500EA

AF:

0.0378

AC:

325

ExAC

AF:

0.106

AC:

12868

Asia WGS

AF:

0.254

AC:

882

AN:

3478

EpiCase

AF:

0.0453

EpiControl

AF:

0.0469

ClinVar

Significance: Likely benign; Affects; association

Submissions summary: Benign:1Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ABCG2-related disorder

Benign:1

Jul 21, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

URIC ACID CONCENTRATION, SERUM, QUANTITATIVE TRAIT LOCUS 1

Other:1

Jan 15, 2012

OMIM

Significance:association

Review Status:no assertion criteria provided

Collection Method:literature only

- -

BLOOD GROUP, JUNIOR SYSTEM

Other:1

Jan 15, 2012

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

1.6

(source)

DANN

Benign

0.054

DEOGEN2

Benign

0.041

.;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00089

LIST_S2

Benign

0.21

T;T;.;T

MetaRNN

Benign

0.0050

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.9

N;N;.;.

PhyloP100

0.21

PrimateAI

Benign

0.32

PROVEAN

Benign

0.69

N;N;N;.

REVEL

Benign

0.18

Sift

Benign

1.0

T;T;D;.

Sift4G

Benign

1.0

T;T;.;.

Polyphen

0.0070

B;B;.;.

Vest4

0.075

MPC

0.030

ClinPred

0.00058

GERP RS

1.5

Varity_R

0.021

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over