NM_004827.3:c.1858G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_004827.3(ABCG2):c.1858G>A(p.Asp620Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00507 in 1,612,956 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 58 hom. )

Consequence

ABCG2
NM_004827.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.81

Publications

42 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 (MetaRNN=0.0064156353).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00332 (506/152276) while in subpopulation SAS AF = 0.0191 (92/4816). AF 95% confidence interval is 0.0159. There are 2 homozygotes in GnomAd4. There are 273 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 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.1858G>A	p.Asp620Asn	missense	Exon 16 of 16	NP_004818.2	Q9UNQ0-1
ABCG2	NM_001348985.1		c.1858G>A	p.Asp620Asn	missense	Exon 17 of 17	NP_001335914.1	Q9UNQ0-1
ABCG2	NM_001348986.2		c.1858G>A	p.Asp620Asn	missense	Exon 16 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.1858G>A	p.Asp620Asn	missense	Exon 16 of 16	ENSP00000237612.3	Q9UNQ0-1
ABCG2	ENST00000515655.5	TSL:1	c.*12G>A		3_prime_UTR	Exon 16 of 16	ENSP00000426917.1	Q9UNQ0-2
ABCG2	ENST00000889086.1		c.1945G>A	p.Asp649Asn	missense	Exon 17 of 17	ENSP00000559145.1

Frequencies

GnomAD3 genomes

AF:

0.00331

AC:

504

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0187

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00485

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00520

AC:

1291

AN:

248078

AF XY:

0.00618

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00164

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00494

Gnomad OTH exome

AF:

0.00328

GnomAD4 exome

AF:

0.00525

AC:

7669

AN:

1460680

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

4191

AN XY:

726528

show subpopulations

African (AFR)

AF:

0.000778

AC:

AN:

33414

American (AMR)

AF:

0.00171

AC:

AN:

44490

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26104

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39678

South Asian (SAS)

AF:

0.0216

AC:

1851

AN:

85792

European-Finnish (FIN)

AF:

0.000637

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00481

AC:

5344

AN:

1111666

Other (OTH)

AF:

0.00451

AC:

272

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

361

722

1084

1445

1806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<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:

0.00332

AC:

506

AN:

152276

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

273

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41570

American (AMR)

AF:

0.00196

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0191

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00485

AC:

330

AN:

68024

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

109

136

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:

0.00440

Hom.:

Bravo

AF:

0.00317

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00554

AC:

673

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00497

EpiControl

AF:

0.00599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.085

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.7

PhyloP100

4.8

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.25

Sift

Benign

0.069

Sift4G

Uncertain

0.036

Polyphen

0.088

Vest4

0.31

MVP

0.72

MPC

0.032

ClinPred

0.024

GERP RS

4.4

Varity_R

0.32

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over