rs3785911

chr17-50690070-A-Cchr17-50690070-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003786.4(ABCC3):c.4476-1022A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,094 control chromosomes in the GnomAD database, including 6,370 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 0.29 (6370 hom., cov: 32)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC3	NM_003786.4	c.4476-1022A>C		intron_variant		ENST00000285238.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC3	ENST00000285238.13	c.4476-1022A>C		intron_variant		1	NM_003786.4	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43413 AN: 151974 Hom.: 6359 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43440 AN: 152094 Hom.: 6370 Cov.: 32 AF XY: 0.280 AC XY: 20822 AN XY: 74332

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.294

Alfa AF: 0.293 Hom.: 5240

Bravo AF: 0.279

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.7
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3785911; hg19: chr17-48767431;