chr4-88113437-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP3BP6BS2

The NM_004827.3(ABCG2):c.1060G>A(p.Gly354Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,613,994 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 8 hom. )

Consequence

ABCG2
NM_004827.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.03

Publications

17 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: Likely_benign. The variant received -4 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 4-88113437-C-T is Benign according to our data. Variant chr4-88113437-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3044880.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 BG gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCG2	NM_004827.3	MANE Select	c.1060G>A	p.Gly354Arg	missense	Exon 9 of 16	NP_004818.2	Q9UNQ0-1
ABCG2	NM_001348985.1		c.1060G>A	p.Gly354Arg	missense	Exon 10 of 17	NP_001335914.1	Q9UNQ0-1
ABCG2	NM_001348986.2		c.1060G>A	p.Gly354Arg	missense	Exon 9 of 16	NP_001335915.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.1060G>A	p.Gly354Arg	missense	Exon 9 of 16	ENSP00000237612.3	Q9UNQ0-1
ABCG2	ENST00000515655.5	TSL:1	c.1060G>A	p.Gly354Arg	missense	Exon 9 of 16	ENSP00000426917.1	Q9UNQ0-2
ABCG2	ENST00000889086.1		c.1147G>A	p.Gly383Arg	missense	Exon 10 of 17	ENSP00000559145.1

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

421

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00415

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00257

AC:

646

AN:

251282

AF XY:

0.00249

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00309

Gnomad NFE exome

AF:

0.00403

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00357

AC:

5219

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00350

AC XY:

2543

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33480

American (AMR)

AF:

0.00179

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

26134

East Asian (EAS)

AF:

0.000126

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00337

AC:

180

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00421

AC:

4680

AN:

1111998

Other (OTH)

AF:

0.00277

AC:

167

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

305

610

914

1219

1524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

360

540

720

900

<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:

0.00277

AC:

421

AN:

152118

Hom.:

Cov.:

AF XY:

0.00247

AC XY:

184

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41508

American (AMR)

AF:

0.00282

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00302

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00415

AC:

282

AN:

67994

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00272

Hom.:

Bravo

AF:

0.00269

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00500

AC:

ExAC

AF:

0.00264

AC:

320

EpiCase

AF:

0.00387

EpiControl

AF:

0.00373

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ABCG2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.049

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.16

M_CAP

Benign

0.026

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.2

PhyloP100

-1.0

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.19

REVEL

Benign

0.088

Sift

Benign

0.30

Sift4G

Benign

0.48

Polyphen

0.052

Vest4

0.12

MutPred

0.35

Gain of MoRF binding (P = 0.0109)

MVP

0.32

MPC

0.033

ClinPred

0.0021

GERP RS

-6.2

Varity_R

0.088

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.62

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.62

Position offset: -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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over