Genetic Variant ABCC3:c.613-22G>A (chr17-50658413-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11

Publications

14 publications found

Variant links:

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]

ABCC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC3	NM_003786.4 link	c.613-22G>A		intron_variant	Intron 5 of 30	ENST00000285238.13	NP_003777.2	O15438-1
ABCC3	NM_001144070.2 link	c.613-22G>A		intron_variant	Intron 5 of 11		NP_001137542.1	O15438-5Q86VN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC3	ENST00000285238.13 link	c.613-22G>A		intron_variant	Intron 5 of 30	1	NM_003786.4	ENSP00000285238.8		O15438-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41628

AN:

151910

Hom.:

5900

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.287

AC XY:

208300

AN XY:

725296

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

14581

29162

43743

58324

72905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10286

20572

30858

41144

51430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.274

AC:

41626

AN:

152028

Hom.:

5897

Cov.:

AF XY:

0.281

AC XY:

20894

AN XY:

74284

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17838

AN:

67936

Other (OTH)

AF:

0.262

AC:

552

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1539

3078

4618

6157

7696

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.016

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over