17-50642254-T-A

Variant names:

• chr17-50642254-T-A
• rs739922
• NM_003786.4:c.45+7273T>A

Variant summary

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

The NM_003786.4(ABCC3):​c.45+7273T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,102 control chromosomes in the GnomAD database, including 13,151 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 0.41 (13151 hom., cov: 33)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 5 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC3	NM_003786.4	c.45+7273T>A		intron_variant	Intron 1 of 30	ENST00000285238.13	NP_003777.2
ABCC3	NM_001144070.2	c.45+7273T>A		intron_variant	Intron 1 of 11		NP_001137542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC3	ENST00000285238.13	c.45+7273T>A		intron_variant	Intron 1 of 30	1	NM_003786.4	ENSP00000285238.8

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62590 AN: 151984 Hom.: 13135 Cov.: 33

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.412 AC: 62644 AN: 152102 Hom.: 13151 Cov.: 33 AF XY: 0.408 AC XY: 30372 AN XY: 74358

African (AFR) AF: 0.424 AC: 17576 AN: 41468

American (AMR) AF: 0.428 AC: 6554 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1450 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5170

South Asian (SAS) AF: 0.340 AC: 1640 AN: 4826

European-Finnish (FIN) AF: 0.408 AC: 4322 AN: 10590

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28571 AN: 67962

Other (OTH) AF: 0.408 AC: 863 AN: 2114

Alfa AF: 0.418 Hom.: 1969

Bravo AF: 0.412

Asia WGS AF: 0.305 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.0
DANN	Benign	0.20
PhyloP100		-1.3
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: rs739922; hg19: chr17-48719615;