17-50634726-C-T

Variant names:

• chr17-50634726-C-T
• rs4793665
• ENST00000746096.1:n.189+4119G>A

Variant summary

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

The ENST00000746096.1(ENSG00000251239):​n.189+4119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 415,796 control chromosomes in the GnomAD database, including 74,465 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 0.59 (26632 hom., cov: 34)
  • Exomes 𝑓: 0.60 (47833 hom.)
• Consequence: ENSG00000251239 ENST00000746096.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 56 publications found

Genes affected

ENSG00000251239 (HGNC:):

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000746096.1. 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
	ABCC3	NM_003786.4	MANE Select	c.-211C>T		upstream_gene	N/A	NP_003777.2
	ABCC3	NM_001144070.2		c.-211C>T		upstream_gene	N/A	NP_001137542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000251239	ENST00000746096.1		n.189+4119G>A		intron	N/A
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.-211C>T		upstream_gene	N/A	ENSP00000285238.8
	ABCC3	ENST00000427699.5	TSL:1	c.-211C>T		upstream_gene	N/A	ENSP00000395160.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89329 AN: 151988 Hom.: 26603 Cov.: 34

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.595 AC: 156957 AN: 263692 Hom.: 47833 AF XY: 0.593 AC XY: 78926 AN XY: 133082

African (AFR) AF: 0.581 AC: 3956 AN: 6812

American (AMR) AF: 0.624 AC: 4024 AN: 6448

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 4040 AN: 8096

East Asian (EAS) AF: 0.887 AC: 18042 AN: 20340

South Asian (SAS) AF: 0.715 AC: 2012 AN: 2814

European-Finnish (FIN) AF: 0.620 AC: 12471 AN: 20114

Middle Eastern (MID) AF: 0.605 AC: 728 AN: 1204

European-Non Finnish (NFE) AF: 0.561 AC: 102240 AN: 182200

Other (OTH) AF: 0.603 AC: 9444 AN: 15664

GnomAD4 genome AF: 0.588 AC: 89402 AN: 152104 Hom.: 26632 Cov.: 34 AF XY: 0.596 AC XY: 44294 AN XY: 74366

African (AFR) AF: 0.578 AC: 24005 AN: 41512

American (AMR) AF: 0.609 AC: 9306 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3470

East Asian (EAS) AF: 0.871 AC: 4469 AN: 5130

South Asian (SAS) AF: 0.694 AC: 3348 AN: 4824

European-Finnish (FIN) AF: 0.631 AC: 6687 AN: 10594

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37767 AN: 67960

Other (OTH) AF: 0.583 AC: 1234 AN: 2116

Alfa AF: 0.428 Hom.: 1097

Bravo AF: 0.589

Asia WGS AF: 0.721 AC: 2508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.3
DANN	Benign	0.83
PhyloP100		-1.0
PromoterAI		-0.27	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4793665; hg19: chr17-48712087; COSMIC: COSV53328058;