chr4-88140113-C-T

Position:

• chr4-88140113-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCG2	NM_004827.3	c.-19-99G>A		intron_variant		ENST00000237612.8	NP_004818.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCG2	ENST00000237612.8	c.-19-99G>A		intron_variant		1	NM_004827.3	ENSP00000237612.3

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

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.364

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

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.342

Alfa AF: 0.355 Hom.: 12423

Bravo AF: 0.313

Asia WGS AF: 0.293 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.46

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: rs1564481; hg19: chr4-89061265;