rs4148416

Positions:

• chr17-50676062-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003786.4(ABCC3):​c.3039C>T​(p.Gly1013=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0681 in 1,614,004 control chromosomes in the GnomAD database, including 4,905 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 0.10 (1068 hom., cov: 32)
  • Exomes 𝑓: 0.065 (3837 hom.)
• Consequence: ABCC3 NM_003786.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-3.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4	c.3039C>T	p.Gly1013=	synonymous_variant	22/31	ENST00000285238.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.3039C>T	p.Gly1013=	synonymous_variant	22/31	1	NM_003786.4	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15488 AN: 152052 Hom.: 1070 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.0782

GnomAD3 exomes AF: 0.0871 AC: 21895 AN: 251378 Hom.: 1282 AF XY: 0.0816 AC XY: 11082 AN XY: 135866

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.0581

Gnomad EAS exome AF: 0.151

Gnomad SAS exome AF: 0.0879

Gnomad FIN exome AF: 0.0497

Gnomad NFE exome AF: 0.0539

Gnomad OTH exome AF: 0.0727

GnomAD4 exome AF: 0.0646 AC: 94422 AN: 1461836 Hom.: 3837 Cov.: 35 AF XY: 0.0646 AC XY: 46993 AN XY: 727222

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.0565

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0868

Gnomad4 FIN exome AF: 0.0520

Gnomad4 NFE exome AF: 0.0544

Gnomad4 OTH exome AF: 0.0716

GnomAD4 genome AF: 0.102 AC: 15496 AN: 152168 Hom.: 1068 Cov.: 32 AF XY: 0.102 AC XY: 7606 AN XY: 74402

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0873

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.0546

Gnomad4 OTH AF: 0.0798

Alfa AF: 0.0666 Hom.: 805

Bravo AF: 0.112

Asia WGS AF: 0.122 AC: 425 AN: 3478

EpiCase AF: 0.0546

EpiControl AF: 0.0554

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.097
DANN	Benign	0.40

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: rs4148416; hg19: chr17-48753423;