4-88109768-C-G

Variant names:

• chr4-88109768-C-G
• rs2622621
• NM_004827.3:c.1195-2502G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004827.3(ABCG2):​c.1195-2502G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,070 control chromosomes in the GnomAD database, including 7,867 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 0.30 (7867 hom., cov: 32)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 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.1195-2502G>C		intron	N/A	NP_004818.2
	ABCG2	NM_001348985.1		c.1195-2502G>C		intron	N/A	NP_001335914.1
	ABCG2	NM_001348986.2		c.1195-2502G>C		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.1195-2502G>C		intron	N/A	ENSP00000237612.3
	ABCG2	ENST00000515655.5	TSL:1	c.1195-2502G>C		intron	N/A	ENSP00000426917.1
	ABCG2	ENST00000650821.1		c.1195-2502G>C		intron	N/A	ENSP00000498246.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46304 AN: 151952 Hom.: 7856 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.305 AC: 46329 AN: 152070 Hom.: 7867 Cov.: 32 AF XY: 0.303 AC XY: 22532 AN XY: 74334

African (AFR) AF: 0.159 AC: 6602 AN: 41500

American (AMR) AF: 0.351 AC: 5358 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1412 AN: 3462

East Asian (EAS) AF: 0.579 AC: 2990 AN: 5160

South Asian (SAS) AF: 0.380 AC: 1833 AN: 4820

European-Finnish (FIN) AF: 0.264 AC: 2794 AN: 10564

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24199 AN: 67970

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.229 Hom.: 668

Bravo AF: 0.308

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.055
DANN	Benign	0.65
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2622621; hg19: chr4-89030920;