chr17-50658413-G-A

Variant names:

• chr17-50658413-G-A
• rs739923
• NM_003786.4:c.613-22G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003786.4(ABCC3):​c.613-22G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,609,368 control chromosomes in the GnomAD database, including 66,436 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 (5897 hom., cov: 32)
  • Exomes 𝑓: 0.28 (60539 hom.)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	NM_003786.4	MANE Select	c.613-22G>A		intron	N/A	NP_003777.2
	ABCC3	NM_001144070.2		c.613-22G>A		intron	N/A	NP_001137542.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.613-22G>A		intron	N/A	ENSP00000285238.8
	ABCC3	ENST00000427699.5	TSL:1	c.613-22G>A		intron	N/A	ENSP00000395160.1
	ABCC3	ENST00000502426.5	TSL:2	n.613-22G>A		intron	N/A	ENSP00000427073.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41628 AN: 151910 Hom.: 5900 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.292 AC: 73387 AN: 251402 AF XY: 0.299

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.274

Gnomad ASJ exome AF: 0.238

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.373

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.283 AC: 412865 AN: 1457340 Hom.: 60539 Cov.: 33 AF XY: 0.287 AC XY: 208300 AN XY: 725296

African (AFR) AF: 0.250 AC: 8345 AN: 33364

American (AMR) AF: 0.275 AC: 12314 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 6280 AN: 26100

East Asian (EAS) AF: 0.244 AC: 9690 AN: 39678

South Asian (SAS) AF: 0.442 AC: 38104 AN: 86140

European-Finnish (FIN) AF: 0.359 AC: 19194 AN: 53416

Middle Eastern (MID) AF: 0.249 AC: 1433 AN: 5758

European-Non Finnish (NFE) AF: 0.271 AC: 300251 AN: 1107928

Other (OTH) AF: 0.286 AC: 17254 AN: 60242

GnomAD4 genome AF: 0.274 AC: 41626 AN: 152028 Hom.: 5897 Cov.: 32 AF XY: 0.281 AC XY: 20894 AN XY: 74284

African (AFR) AF: 0.253 AC: 10484 AN: 41478

American (AMR) AF: 0.265 AC: 4042 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5168

South Asian (SAS) AF: 0.460 AC: 2220 AN: 4822

European-Finnish (FIN) AF: 0.383 AC: 4051 AN: 10568

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17838 AN: 67936

Other (OTH) AF: 0.262 AC: 552 AN: 2104

Alfa AF: 0.263 Hom.: 15741

Bravo AF: 0.262

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.016
DANN	Benign	0.72
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs739923; hg19: chr17-48735774; COSMIC: COSV53318865; COSMIC: COSV53318865;