rs1051640

Variant names:

• chr17-50691125-A-G
• rs1051640
• NM_003786.4:c.4509A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003786.4(ABCC3):​c.4509A>G​(p.Glu1503Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,030 control chromosomes in the GnomAD database, including 22,849 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 0.14 (1701 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21148 hom.)
• Consequence: ABCC3 NM_003786.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 38 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=1.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC3	NM_003786.4	c.4509A>G	p.Glu1503Glu	synonymous_variant	Exon 31 of 31	ENST00000285238.13	NP_003777.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC3	ENST00000285238.13	c.4509A>G	p.Glu1503Glu	synonymous_variant	Exon 31 of 31	1	NM_003786.4	ENSP00000285238.8

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21543 AN: 152118 Hom.: 1703 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.144 AC: 36104 AN: 251430 AF XY: 0.145

Gnomad AFR exome AF: 0.0859

Gnomad AMR exome AF: 0.0866

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.0543

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.165 AC: 241151 AN: 1460794 Hom.: 21148 Cov.: 31 AF XY: 0.163 AC XY: 118785 AN XY: 726750

African (AFR) AF: 0.0847 AC: 2835 AN: 33460

American (AMR) AF: 0.0904 AC: 4041 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4812 AN: 26128

East Asian (EAS) AF: 0.0459 AC: 1824 AN: 39698

South Asian (SAS) AF: 0.102 AC: 8769 AN: 86238

European-Finnish (FIN) AF: 0.192 AC: 10255 AN: 53402

Middle Eastern (MID) AF: 0.112 AC: 646 AN: 5764

European-Non Finnish (NFE) AF: 0.179 AC: 198361 AN: 1111034

Other (OTH) AF: 0.159 AC: 9608 AN: 60348

GnomAD4 genome AF: 0.142 AC: 21550 AN: 152236 Hom.: 1701 Cov.: 32 AF XY: 0.140 AC XY: 10438 AN XY: 74440

African (AFR) AF: 0.0868 AC: 3606 AN: 41544

American (AMR) AF: 0.127 AC: 1937 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3470

East Asian (EAS) AF: 0.0567 AC: 294 AN: 5184

South Asian (SAS) AF: 0.104 AC: 501 AN: 4828

European-Finnish (FIN) AF: 0.179 AC: 1901 AN: 10596

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12129 AN: 68000

Other (OTH) AF: 0.151 AC: 320 AN: 2114

Alfa AF: 0.163 Hom.: 8227

Bravo AF: 0.136

Asia WGS AF: 0.0780 AC: 271 AN: 3478

EpiCase AF: 0.180

EpiControl AF: 0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		1.9
Mutation Taster		=88/12	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1051640; hg19: chr17-48768486; COSMIC: COSV108069614; COSMIC: COSV108069614;