rs140207606

Variant names:

• chr4-88118244-G-A
• rs140207606
• NM_004827.3:c.706C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-88118244-G-A
• chr4-88118244-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004827.3(ABCG2):​c.706C>T​(p.Arg236*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000253 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as association (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: ABCG2 NM_004827.3 stop_gained
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 1.76

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.706C>T	p.Arg236*	stop_gained	Exon 7 of 16	ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.706C>T	p.Arg236*	stop_gained	Exon 7 of 16	1	NM_004827.3	ENSP00000237612.3
ABCG2	ENST00000515655.5	c.706C>T	p.Arg236*	stop_gained	Exon 7 of 16	1		ENSP00000426917.1
ABCG2	ENST00000650821.1	c.706C>T	p.Arg236*	stop_gained	Exon 8 of 17			ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000311 AC: 78 AN: 251158 AF XY: 0.000346

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000259 AC: 378 AN: 1461722 Hom.: 0 Cov.: 30 AF XY: 0.000285 AC XY: 207 AN XY: 727156

Gnomad4 AFR exome AF: 0.000209 AC: 7 AN: 33476

Gnomad4 AMR exome AF: 0.0000671 AC: 3 AN: 44708

Gnomad4 ASJ exome AF: 0.00126 AC: 33 AN: 26130

Gnomad4 EAS exome AF: 0.000328 AC: 13 AN: 39688

Gnomad4 SAS exome AF: 0.000267 AC: 23 AN: 86240

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53412

Gnomad4 NFE exome AF: 0.000253 AC: 281 AN: 1111912

Gnomad4 Remaining exome AF: 0.000298 AC: 18 AN: 60390

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74462

Gnomad4 AFR AF: 0.000193 AC: 0.000192539 AN: 0.000192539

Gnomad4 AMR AF: 0.0000654 AC: 0.0000653595 AN: 0.0000653595

Gnomad4 ASJ AF: 0.000576 AC: 0.000576037 AN: 0.000576037

Gnomad4 EAS AF: 0.000193 AC: 0.000192678 AN: 0.000192678

Gnomad4 SAS AF: 0.000208 AC: 0.000207555 AN: 0.000207555

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000250 AC: 0.000249897 AN: 0.000249897

Gnomad4 OTH AF: 0.000473 AC: 0.000473037 AN: 0.000473037

Alfa AF: 0.000340 Hom.: 0

Bravo AF: 0.000223

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.000491

EpiControl AF: 0.000237

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

BLOOD GROUP, JUNIOR SYSTEM Other:1

Mar 18, 2013

OMIM

Significance: association

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.79	D
Vest4		0.79
GERP RS		3.4
Mutation Taster		=40/160	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs140207606; hg19: chr4-89039396; COSMIC: COSV52946159;