NM_003786.4:c.46-7678G>A

Variant names:

• chr17-50648154-G-A
• rs4794173
• NM_003786.4:c.46-7678G>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.46-7678G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,064 control chromosomes in the GnomAD database, including 32,008 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 (32008 hom., cov: 33)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	NM_003786.4	MANE Select	c.46-7678G>A		intron	N/A	NP_003777.2
	ABCC3	NM_001144070.2		c.46-7678G>A		intron	N/A	NP_001137542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.46-7678G>A		intron	N/A	ENSP00000285238.8
	ABCC3	ENST00000427699.5	TSL:1	c.46-7678G>A		intron	N/A	ENSP00000395160.1
	ABCC3	ENST00000502426.5	TSL:2	n.46-7678G>A		intron	N/A	ENSP00000427073.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97113 AN: 151946 Hom.: 31979 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.639 AC: 97184 AN: 152064 Hom.: 32008 Cov.: 33 AF XY: 0.638 AC XY: 47406 AN XY: 74336

African (AFR) AF: 0.490 AC: 20288 AN: 41440

American (AMR) AF: 0.584 AC: 8931 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2321 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2877 AN: 5172

South Asian (SAS) AF: 0.677 AC: 3268 AN: 4824

European-Finnish (FIN) AF: 0.750 AC: 7935 AN: 10574

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49370 AN: 67982

Other (OTH) AF: 0.657 AC: 1387 AN: 2110

Alfa AF: 0.695 Hom.: 117999

Bravo AF: 0.619

Asia WGS AF: 0.570 AC: 1980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.34
PhyloP100		-0.22
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: rs4794173; hg19: chr17-48725515;