17-50683744-C-T

Variant names:

• chr17-50683744-C-T
• rs2277624
• NM_003786.4:c.3942C>T

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.3942C>T​(p.His1314His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 1,604,262 control chromosomes in the GnomAD database, including 43,505 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 0.27 (5706 hom., cov: 31)
  • Exomes 𝑓: 0.23 (37799 hom.)
• Consequence: ABCC3 NM_003786.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.25
• Publications: 35 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=-0.7).
• BP7: Synonymous conserved (PhyloP=-4.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC3	NM_003786.4	c.3942C>T	p.His1314His	synonymous_variant	Exon 27 of 31	ENST00000285238.13	NP_003777.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC3	ENST00000285238.13	c.3942C>T	p.His1314His	synonymous_variant	Exon 27 of 31	1	NM_003786.4	ENSP00000285238.8

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40413 AN: 151950 Hom.: 5690 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.250

GnomAD2 exomes AF: 0.243 AC: 58710 AN: 241154 AF XY: 0.237

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.256

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.225 AC: 327334 AN: 1452194 Hom.: 37799 Cov.: 34 AF XY: 0.224 AC XY: 161795 AN XY: 722420

African (AFR) AF: 0.366 AC: 11970 AN: 32686

American (AMR) AF: 0.282 AC: 11846 AN: 42068

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5589 AN: 25722

East Asian (EAS) AF: 0.205 AC: 8042 AN: 39176

South Asian (SAS) AF: 0.214 AC: 18265 AN: 85250

European-Finnish (FIN) AF: 0.241 AC: 12817 AN: 53120

Middle Eastern (MID) AF: 0.196 AC: 1122 AN: 5710

European-Non Finnish (NFE) AF: 0.220 AC: 243820 AN: 1108496

Other (OTH) AF: 0.231 AC: 13863 AN: 59966

GnomAD4 genome AF: 0.266 AC: 40472 AN: 152068 Hom.: 5706 Cov.: 31 AF XY: 0.266 AC XY: 19753 AN XY: 74344

African (AFR) AF: 0.355 AC: 14712 AN: 41462

American (AMR) AF: 0.282 AC: 4301 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1274 AN: 5154

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4824

European-Finnish (FIN) AF: 0.225 AC: 2382 AN: 10600

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15107 AN: 67966

Other (OTH) AF: 0.250 AC: 528 AN: 2108

Alfa AF: 0.235 Hom.: 20498

Bravo AF: 0.276

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.14
DANN	Benign	0.41
PhyloP100		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	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: rs2277624; hg19: chr17-48761105; COSMIC: COSV53318907; COSMIC: COSV53318907;