rs733392

Positions:

• chr17-50659042-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.675-195G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 550,854 control chromosomes in the GnomAD database, including 22,221 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 (5580 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16641 hom.)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC3	NM_003786.4	c.675-195G>A		intron_variant		ENST00000285238.13	NP_003777.2
ABCC3	NM_001144070.2	c.675-195G>A		intron_variant			NP_001137542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC3	ENST00000285238.13	c.675-195G>A		intron_variant		1	NM_003786.4	ENSP00000285238.8

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40303 AN: 151882 Hom.: 5586 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.279 AC: 111380 AN: 398856 Hom.: 16641 AF XY: 0.285 AC XY: 58906 AN XY: 206562

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.226

Gnomad4 SAS exome AF: 0.406

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.265 AC: 40295 AN: 151998 Hom.: 5580 Cov.: 32 AF XY: 0.271 AC XY: 20118 AN XY: 74282

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.243

Alfa AF: 0.268 Hom.: 11584

Bravo AF: 0.252

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.55

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: rs733392; hg19: chr17-48736403;