rs2622628

Positions:

• chr4-88108100-A-C
• chr4-88108100-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004827.3(ABCG2):​c.1195-834T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,166 control chromosomes in the GnomAD database, including 54,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.83 (54676 hom., cov: 33)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0590

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-88108100-A-C is Benign according to our data. Variant chr4-88108100-A-C is described in ClinVar as [Benign]. Clinvar id is 1265403.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.1195-834T>G		intron_variant		ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.1195-834T>G		intron_variant		1	NM_004827.3	ENSP00000237612	P1
ABCG2	ENST00000515655.5	c.1195-834T>G		intron_variant		1		ENSP00000426917
ABCG2	ENST00000650821.1	c.1195-834T>G		intron_variant				ENSP00000498246	P1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126350 AN: 152048 Hom.: 54657 Cov.: 33

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.981

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.940

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.856

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

GnomAD4 genome AF: 0.831 AC: 126417 AN: 152166 Hom.: 54676 Cov.: 33 AF XY: 0.829 AC XY: 61708 AN XY: 74400

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.981

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.940

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.853

Alfa AF: 0.942 Hom.: 93792

Bravo AF: 0.807

Asia WGS AF: 0.816 AC: 2840 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 09, 2019

This variant is associated with the following publications: (PMID: 28930109) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.3
DANN	Benign	0.49

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: rs2622628; hg19: chr4-89029252;