chr17-50659042-G-A

Variant names:

• chr17-50659042-G-A
• rs733392
• NM_003786.4:c.675-195G>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.675-195G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 550,854 control chromosomes in the GnomAD database, including 22,221 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 (5580 hom., cov: 32)
  • Exomes 𝑓: 0.28 (16641 hom.)
• Consequence: ABCC3 NM_003786.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 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.675-195G>A		intron	N/A	NP_003777.2
	ABCC3	NM_001144070.2		c.675-195G>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.675-195G>A		intron	N/A	ENSP00000285238.8
	ABCC3	ENST00000427699.5	TSL:1	c.675-195G>A		intron	N/A	ENSP00000395160.1
	ABCC3	ENST00000502426.5	TSL:2	n.675-140G>A		intron	N/A	ENSP00000427073.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40303 AN: 151882 Hom.: 5586 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.279 AC: 111380 AN: 398856 Hom.: 16641 AF XY: 0.285 AC XY: 58906 AN XY: 206562

African (AFR) AF: 0.216 AC: 2411 AN: 11172

American (AMR) AF: 0.258 AC: 3907 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 2702 AN: 11132

East Asian (EAS) AF: 0.226 AC: 5679 AN: 25162

South Asian (SAS) AF: 0.406 AC: 12922 AN: 31844

European-Finnish (FIN) AF: 0.341 AC: 8027 AN: 23564

Middle Eastern (MID) AF: 0.217 AC: 361 AN: 1664

European-Non Finnish (NFE) AF: 0.270 AC: 69321 AN: 257058

Other (OTH) AF: 0.274 AC: 6050 AN: 22106

GnomAD4 genome AF: 0.265 AC: 40295 AN: 151998 Hom.: 5580 Cov.: 32 AF XY: 0.271 AC XY: 20118 AN XY: 74282

African (AFR) AF: 0.221 AC: 9163 AN: 41486

American (AMR) AF: 0.251 AC: 3840 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 821 AN: 3466

East Asian (EAS) AF: 0.233 AC: 1200 AN: 5148

South Asian (SAS) AF: 0.441 AC: 2124 AN: 4820

European-Finnish (FIN) AF: 0.378 AC: 3991 AN: 10572

Middle Eastern (MID) AF: 0.166 AC: 48 AN: 290

European-Non Finnish (NFE) AF: 0.270 AC: 18347 AN: 67910

Other (OTH) AF: 0.243 AC: 513 AN: 2108

Alfa AF: 0.266 Hom.: 18649

Bravo AF: 0.252

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.55
PhyloP100		-0.68
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: rs733392; hg19: chr17-48736403;