rs2199936

Positions:

• chr4-88124179-A-G
• chr4-88124179-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004827.3(ABCG2):​c.532-2387T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,158 control chromosomes in the GnomAD database, including 58,945 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (58945 hom., cov: 32)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.532-2387T>C		intron_variant		ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.532-2387T>C		intron_variant		1	NM_004827.3	ENSP00000237612	P1
ABCG2	ENST00000515655.5	c.532-2387T>C		intron_variant		1		ENSP00000426917
ABCG2	ENST00000650821.1	c.532-2387T>C		intron_variant				ENSP00000498246	P1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133593 AN: 152040 Hom.: 58904 Cov.: 32

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.691

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.939

Gnomad NFE AF: 0.890

Gnomad OTH AF: 0.893

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.879 AC: 133689 AN: 152158 Hom.: 58945 Cov.: 32 AF XY: 0.879 AC XY: 65385 AN XY: 74394

Gnomad4 AFR AF: 0.873

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.690

Gnomad4 SAS AF: 0.904

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.890

Gnomad4 OTH AF: 0.892

Alfa AF: 0.886 Hom.: 9866

Bravo AF: 0.869

Asia WGS AF: 0.818 AC: 2846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2199936; hg19: chr4-89045331;