4-88104957-C-T

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.1277+2227G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,120 control chromosomes in the GnomAD database, including 45,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.71 (45173 hom., cov: 31)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.816

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=-0.87).
• BP6: Variant 4-88104957-C-T is Benign according to our data. Variant chr4-88104957-C-T is described in ClinVar as [Benign]. Clinvar id is 1239257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCG2	NM_004827.3	c.1277+2227G>A		intron_variant		ENST00000237612.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCG2	ENST00000237612.8	c.1277+2227G>A		intron_variant		1	NM_004827.3	P1
ABCG2	ENST00000515655.5	c.1277+2227G>A		intron_variant		1
ABCG2	ENST00000650821.1	c.1277+2227G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108331 AN: 152002 Hom.: 45172 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.729

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.928

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.930

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.712 AC: 108359 AN: 152120 Hom.: 45173 Cov.: 31 AF XY: 0.715 AC XY: 53175 AN XY: 74388

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.928

Gnomad4 NFE AF: 0.930

Gnomad4 OTH AF: 0.747

Alfa AF: 0.888 Hom.: 111443

Bravo AF: 0.677

Asia WGS AF: 0.766 AC: 2664 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	-0.87
Cadd	Benign	2.7
Dann	Benign	0.24

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: rs2725264; hg19: chr4-89026109;