4-88104957-C-T

Variant names:

• chr4-88104957-C-T
• rs2725264
• NM_004827.3:c.1277+2227G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004827.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_004827.3	MANE Select	c.1277+2227G>A		intron	N/A	NP_004818.2
	ABCG2	NM_001348985.1		c.1277+2227G>A		intron	N/A	NP_001335914.1
	ABCG2	NM_001348986.2		c.1277+2227G>A		intron	N/A	NP_001335915.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.1277+2227G>A		intron	N/A	ENSP00000237612.3
	ABCG2	ENST00000515655.5	TSL:1	c.1277+2227G>A		intron	N/A	ENSP00000426917.1
	ABCG2	ENST00000650821.1		c.1277+2227G>A		intron	N/A	ENSP00000498246.1

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

African (AFR) AF: 0.249 AC: 10326 AN: 41432

American (AMR) AF: 0.729 AC: 11138 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3140 AN: 3468

East Asian (EAS) AF: 0.802 AC: 4155 AN: 5180

South Asian (SAS) AF: 0.814 AC: 3920 AN: 4818

European-Finnish (FIN) AF: 0.928 AC: 9844 AN: 10610

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.930 AC: 63292 AN: 68024

Other (OTH) AF: 0.747 AC: 1577 AN: 2112

Alfa AF: 0.839 Hom.: 150649

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

Jan 09, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.24
PhyloP100		0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2725264; hg19: chr4-89026109;