Variant rs72552713 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_004827.3(ABCG2):c.376C>T(p.Gln126Ter) variant causes a stop gained, splice region change. The variant allele was found at a frequency of 0.000377 in 1,611,534 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as association (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 9 hom. )

Consequence

ABCG2
NM_004827.3 stop_gained, splice_region

Scores

Splicing: ADA: 0.9972

Clinical Significance

association no assertion criteria provided O:2

Conservation

PhyloP100: 6.08

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM4

Stoplost variant in NM_004827.3 Downstream stopcodon found after 44 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG2	NM_004827.3 linkuse as main transcript	c.376C>T	p.Gln126Ter	stop_gained, splice_region_variant	4/16	ENST00000237612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG2	ENST00000237612.8 linkuse as main transcript	c.376C>T	p.Gln126Ter	stop_gained, splice_region_variant	4/16	1	NM_004827.3	P1	Q9UNQ0-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00655

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000396

AC:

AN:

250314

Hom.:

AF XY:

0.000355

AC XY:

AN XY:

135252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00518

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000493

GnomAD4 exome

AF:

0.000392

AC:

572

AN:

1459228

Hom.:

Cov.:

AF XY:

0.000375

AC XY:

272

AN XY:

725954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0140

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000230

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00656

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000369

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.000469

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Uric acid concentration, serum, quantitative trait locus 1

Other:1

association, no assertion criteria provided

literature only

OMIM

Jan 15, 2012

- -

Blood group, Junior system

Other:1

association, no assertion criteria provided

literature only

OMIM

Oct 22, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.66

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.1

FATHMM_MKL

Pathogenic

0.99

MutationTaster

Benign

1.0

A;A

Vest4

0.97

GERP RS

5.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.92

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over