rs739923

chr17-50658413-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003786.4(ABCC3):c.613-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,609,368 control chromosomes in the GnomAD database, including 66,436 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 0.27 (5897 hom., cov: 32)
  • Exomes 𝑓: 0.28 (60539 hom.)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

Genes affected

ABCC3 (HGNC:54): (ATP binding cassette subfamily C member 3) The protein encoded by this gene is a member of 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 MRP subfamily which is involved in multi-drug resistance. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4	c.613-22G>A		intron_variant		ENST00000285238.13
ABCC3	NM_001144070.2	c.613-22G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.613-22G>A		intron_variant		1	NM_003786.4	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41628 AN: 151910 Hom.: 5900 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.267

GnomAD3 exomes AF: 0.292 AC: 73387 AN: 251402 Hom.: 11422 AF XY: 0.299 AC XY: 40683 AN XY: 135868

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.242

Gnomad SAS exome AF: 0.446

Gnomad FIN exome AF: 0.373

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.283 AC: 412865 AN: 1457340 Hom.: 60539 Cov.: 33 AF XY: 0.287 AC XY: 208300 AN XY: 725296

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.359

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.274 AC: 41626 AN: 152028 Hom.: 5897 Cov.: 32 AF XY: 0.281 AC XY: 20894 AN XY: 74284

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.262

Alfa AF: 0.265 Hom.: 7336

Bravo AF: 0.262

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.016
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs739923; hg19: chr17-48735774; COSMIC: COSV53318865; COSMIC: COSV53318865;