rs2277624

chr17-50683744-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.3942C>T(p.His1314=) 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

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=-0.7).
• 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/exons	MANE	UniProt
ABCC3	NM_003786.4	c.3942C>T	p.His1314=	synonymous_variant	27/31	ENST00000285238.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.3942C>T	p.His1314=	synonymous_variant	27/31	1	NM_003786.4	P1
ABCC3	ENST00000503337.1	n.1136C>T		non_coding_transcript_exon_variant	2/6	1
ABCC3	ENST00000502426.5	c.*2613C>T		3_prime_UTR_variant, NMD_transcript_variant	26/30	2
ABCC3	ENST00000505699.5	c.*374C>T		3_prime_UTR_variant, NMD_transcript_variant	26/30	2

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

GnomAD3 exomes AF: 0.243 AC: 58710 AN: 241154 Hom.: 7476 AF XY: 0.237 AC XY: 31003 AN XY: 130860

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 SAS exome AF: 0.216

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

Gnomad4 AFR exome AF: 0.366

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.231

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

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.250

Alfa AF: 0.228 Hom.: 9728

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2277624; hg19: chr17-48761105; COSMIC: COSV53318907; COSMIC: COSV53318907;