NM_003786.4:c.4476-1022A>C

Variant names:

• chr17-50690070-A-C
• rs3785911
• NM_003786.4:c.4476-1022A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	NM_003786.4	MANE Select	c.4476-1022A>C		intron	N/A	NP_003777.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC3	ENST00000285238.13	TSL:1 MANE Select	c.4476-1022A>C		intron	N/A	ENSP00000285238.8	O15438-1
	ABCC3	ENST00000503337.1	TSL:1	n.1670-1022A>C		intron	N/A
	ABCC3	ENST00000871907.1		c.4581-1022A>C		intron	N/A	ENSP00000541966.1

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

African (AFR) AF: 0.311 AC: 12885 AN: 41488

American (AMR) AF: 0.214 AC: 3265 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3470

East Asian (EAS) AF: 0.163 AC: 843 AN: 5162

South Asian (SAS) AF: 0.271 AC: 1303 AN: 4812

European-Finnish (FIN) AF: 0.268 AC: 2841 AN: 10590

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20507 AN: 67964

Other (OTH) AF: 0.294 AC: 621 AN: 2112

Alfa AF: 0.293 Hom.: 6342

Bravo AF: 0.279

Asia WGS AF: 0.209 AC: 726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3785911; hg19: chr17-48767431;