rs4794173

chr17-50648154-G-Achr17-50648154-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4	c.46-7678G>A		intron_variant		ENST00000285238.13
ABCC3	NM_001144070.2	c.46-7678G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.46-7678G>A		intron_variant		1	NM_003786.4	P1

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

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.657

Alfa AF: 0.711 Hom.: 77987

Bravo AF: 0.619

Asia WGS AF: 0.570 AC: 1980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.0
Dann	Benign	0.34

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: rs4794173; hg19: chr17-48725515;