chr17-50676062-C-T

Variant names:

• chr17-50676062-C-T
• rs4148416
• NM_003786.4:c.3039C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003786.4(ABCC3):​c.3039C>T​(p.Gly1013Gly) 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
• Publications: 41 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.026).
• 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 rank	MANE	Protein	UniProt
ABCC3	NM_003786.4	c.3039C>T	p.Gly1013Gly	synonymous_variant	Exon 22 of 31	ENST00000285238.13	NP_003777.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC3	ENST00000285238.13	c.3039C>T	p.Gly1013Gly	synonymous_variant	Exon 22 of 31	1	NM_003786.4	ENSP00000285238.8

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

GnomAD2 exomes AF: 0.0871 AC: 21895 AN: 251378 AF XY: 0.0816

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 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

African (AFR) AF: 0.198 AC: 6628 AN: 33470

American (AMR) AF: 0.139 AC: 6207 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 1477 AN: 26136

East Asian (EAS) AF: 0.113 AC: 4481 AN: 39700

South Asian (SAS) AF: 0.0868 AC: 7485 AN: 86256

European-Finnish (FIN) AF: 0.0520 AC: 2775 AN: 53414

Middle Eastern (MID) AF: 0.0905 AC: 521 AN: 5760

European-Non Finnish (NFE) AF: 0.0544 AC: 60521 AN: 1111992

Other (OTH) AF: 0.0716 AC: 4327 AN: 60394

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

African (AFR) AF: 0.191 AC: 7927 AN: 41476

American (AMR) AF: 0.109 AC: 1670 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3470

East Asian (EAS) AF: 0.139 AC: 720 AN: 5174

South Asian (SAS) AF: 0.0873 AC: 421 AN: 4824

European-Finnish (FIN) AF: 0.0496 AC: 526 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0546 AC: 3712 AN: 68000

Other (OTH) AF: 0.0798 AC: 168 AN: 2106

Alfa AF: 0.0761 Hom.: 1792

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
PhyloP100		-3.3
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: rs4148416; hg19: chr17-48753423;