dbSNP rs7193955: ABCC12:p.Arg1117Cys (chr16-48088671-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001393799.1(ABCC12):c.-30C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,613,926 control chromosomes in the GnomAD database, including 469,291 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 0.62 ( 33860 hom., cov: 33)

Exomes 𝑓: 0.76 ( 435431 hom. )

Consequence

ABCC12
NM_001393799.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.155

Variant links:

Genes affected

ABCC12 (HGNC:14640): (ATP binding cassette subfamily C member 12) This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two ATP-binding domains and 12 transmembrane regions. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies: ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White. This gene is a member of the MRP subfamily which is involved in multi-drug resistance. This gene and another subfamily member are arranged head-to-tail on chromosome 16q12.1. Increased expression of this gene is associated with breast cancer. [provided by RefSeq, Jul 2008]

ABCC12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.6479676E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC12	NM_001393797.1 link	c.3349C>T	p.Arg1117Cys	missense_variant	Exon 26 of 31	ENST00000311303.8	NP_001380726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC12	ENST00000311303.8 link	c.3349C>T	p.Arg1117Cys	missense_variant	Exon 26 of 31	1	NM_001393797.1	ENSP00000311030.4		A0A8J8YUR7

Frequencies

GnomAD3 genomes

AF:

0.616

AC:

93701

AN:

152052

Hom.:

33866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.876

Gnomad AMR

AF:

0.631

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.895

Gnomad SAS

AF:

0.801

Gnomad FIN

AF:

0.840

Gnomad MID

AF:

0.734

Gnomad NFE

AF:

0.777

Gnomad OTH

AF:

0.648

GnomAD3 exomes

AF:

0.722

AC:

181460

AN:

251320

Hom.:

69363

AF XY:

0.743

AC XY:

100886

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.529

Gnomad ASJ exome

AF:

0.786

Gnomad EAS exome

AF:

0.892

Gnomad SAS exome

AF:

0.807

Gnomad FIN exome

AF:

0.839

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

AF:

0.765

AC:

1117596

AN:

1461756

Hom.:

435431

Cov.:

AF XY:

0.769

AC XY:

558851

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.541

Gnomad4 ASJ exome

AF:

0.792

Gnomad4 EAS exome

AF:

0.916

Gnomad4 SAS exome

AF:

0.807

Gnomad4 FIN exome

AF:

0.838

Gnomad4 NFE exome

AF:

0.779

Gnomad4 OTH exome

AF:

0.747

GnomAD4 genome

AF:

0.616

AC:

93696

AN:

152170

Hom.:

33860

Cov.:

AF XY:

0.623

AC XY:

46369

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.630

Gnomad4 ASJ

AF:

0.790

Gnomad4 EAS

AF:

0.894

Gnomad4 SAS

AF:

0.803

Gnomad4 FIN

AF:

0.840

Gnomad4 NFE

AF:

0.778

Gnomad4 OTH

AF:

0.642

Alfa

AF:

0.747

Hom.:

84777

Bravo

AF:

0.580

TwinsUK

AF:

0.778

AC:

2886

ALSPAC

AF:

0.785

AC:

3027

ESP6500AA

AF:

0.232

AC:

1020

ESP6500EA

AF:

0.783

AC:

6730

ExAC

AF:

0.719

AC:

87276

Asia WGS

AF:

0.716

AC:

2493

AN:

3478

EpiCase

AF:

0.775

EpiControl

AF:

0.766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.5

DANN

Uncertain

0.98

DEOGEN2

Benign

0.093

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.20

MetaRNN

Benign

0.0000036

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.14

Sift

Benign

0.032

Sift4G

Uncertain

0.054

Polyphen

0.0040

Vest4

0.032

MPC

0.19

ClinPred

0.023

GERP RS

2.7

Varity_R

0.10

gMVP

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over