17-50656454-T-C

Variant names:

• chr17-50656454-T-C
• rs4148412
• NM_003786.4:c.223-248T>C

Variant summary

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

The NM_003786.4(ABCC3):​c.223-248T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,112 control chromosomes in the GnomAD database, including 31,394 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 0.64 (31394 hom., cov: 33)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	NM_003786.4	MANE Select	c.223-248T>C		intron	N/A	NP_003777.2
	ABCC3	NM_001144070.2		c.223-248T>C		intron	N/A	NP_001137542.1	O15438-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.223-248T>C		intron	N/A	ENSP00000285238.8	O15438-1
	ABCC3	ENST00000427699.5	TSL:1	c.223-248T>C		intron	N/A	ENSP00000395160.1	O15438-5
	ABCC3	ENST00000871907.1		c.223-248T>C		intron	N/A	ENSP00000541966.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97299 AN: 151994 Hom.: 31374 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.640 AC: 97361 AN: 152112 Hom.: 31394 Cov.: 33 AF XY: 0.645 AC XY: 47948 AN XY: 74374

African (AFR) AF: 0.574 AC: 23810 AN: 41482

American (AMR) AF: 0.726 AC: 11100 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1931 AN: 3470

East Asian (EAS) AF: 0.731 AC: 3780 AN: 5170

South Asian (SAS) AF: 0.760 AC: 3670 AN: 4826

European-Finnish (FIN) AF: 0.693 AC: 7331 AN: 10580

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43684 AN: 67974

Other (OTH) AF: 0.623 AC: 1318 AN: 2114

Alfa AF: 0.645 Hom.: 97635

Bravo AF: 0.639

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.47
PhyloP100		-1.2
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: rs4148412; hg19: chr17-48733815;