4-88140113-C-T

Variant names:

• chr4-88140113-C-T
• rs1564481
• NM_004827.3:c.-19-99G>A

Variant summary

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

The NM_004827.3(ABCG2):​c.-19-99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 992,404 control chromosomes in the GnomAD database, including 68,112 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 0.32 (8276 hom., cov: 33)
  • Exomes 𝑓: 0.38 (59836 hom.)
• Consequence: ABCG2 NM_004827.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32
• Publications: 22 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	NM_004827.3	MANE Select	c.-19-99G>A		intron	N/A	NP_004818.2	Q9UNQ0-1
	ABCG2	NM_001348985.1		c.-19-99G>A		intron	N/A	NP_001335914.1	Q9UNQ0-1
	ABCG2	NM_001348986.2		c.-19-99G>A		intron	N/A	NP_001335915.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCG2	ENST00000237612.8	TSL:1 MANE Select	c.-19-99G>A		intron	N/A	ENSP00000237612.3	Q9UNQ0-1
	ABCG2	ENST00000515655.5	TSL:1	c.-19-99G>A		intron	N/A	ENSP00000426917.1	Q9UNQ0-2
	ABCG2	ENST00000503830.2	TSL:1	c.-19-99G>A		intron	N/A	ENSP00000426934.2	F8S0F2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48986 AN: 151896 Hom.: 8273 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.376 AC: 316119 AN: 840390 Hom.: 59836 AF XY: 0.377 AC XY: 160395 AN XY: 424970

African (AFR) AF: 0.216 AC: 4203 AN: 19472

American (AMR) AF: 0.305 AC: 7210 AN: 23618

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 7032 AN: 17308

East Asian (EAS) AF: 0.332 AC: 10883 AN: 32788

South Asian (SAS) AF: 0.391 AC: 21445 AN: 54914

European-Finnish (FIN) AF: 0.348 AC: 15051 AN: 43194

Middle Eastern (MID) AF: 0.320 AC: 904 AN: 2828

European-Non Finnish (NFE) AF: 0.387 AC: 235347 AN: 607736

Other (OTH) AF: 0.364 AC: 14044 AN: 38532

GnomAD4 genome AF: 0.322 AC: 48997 AN: 152014 Hom.: 8276 Cov.: 33 AF XY: 0.319 AC XY: 23688 AN XY: 74286

African (AFR) AF: 0.223 AC: 9225 AN: 41450

American (AMR) AF: 0.317 AC: 4840 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1379 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1473 AN: 5172

South Asian (SAS) AF: 0.376 AC: 1808 AN: 4814

European-Finnish (FIN) AF: 0.335 AC: 3532 AN: 10540

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25496 AN: 67968

Other (OTH) AF: 0.342 AC: 723 AN: 2112

Alfa AF: 0.351 Hom.: 27444

Bravo AF: 0.313

Asia WGS AF: 0.293 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.46
PhyloP100		-2.3
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: rs1564481; hg19: chr4-89061265;