16-48141324-G-T

Variant names:

• chr16-48141324-G-T
• rs16945874
• NM_001393797.1:c.305C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393797.1(ABCC12):​c.305C>A​(p.Ala102Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,614,038 control chromosomes in the GnomAD database, including 9,511 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (3263 hom., cov: 32)
  • Exomes 𝑓: 0.076 (6248 hom.)
• Consequence: ABCC12 NM_001393797.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704
• Publications: 21 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003940195).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC12	NM_001393797.1	c.305C>A	p.Ala102Glu	missense_variant	Exon 5 of 31	ENST00000311303.8	NP_001380726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC12	ENST00000311303.8	c.305C>A	p.Ala102Glu	missense_variant	Exon 5 of 31	1	NM_001393797.1	ENSP00000311030.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23990 AN: 152082 Hom.: 3248 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0248

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0783

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.0843 AC: 21201 AN: 251422 AF XY: 0.0785

Gnomad AFR exome AF: 0.373

Gnomad AMR exome AF: 0.0525

Gnomad ASJ exome AF: 0.0593

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.0799

Gnomad OTH exome AF: 0.0752

GnomAD4 exome AF: 0.0757 AC: 110722 AN: 1461838 Hom.: 6248 Cov.: 32 AF XY: 0.0739 AC XY: 53705 AN XY: 727216

African (AFR) AF: 0.373 AC: 12483 AN: 33470

American (AMR) AF: 0.0564 AC: 2521 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 1553 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.0276 AC: 2382 AN: 86258

European-Finnish (FIN) AF: 0.108 AC: 5748 AN: 53416

Middle Eastern (MID) AF: 0.0959 AC: 553 AN: 5768

European-Non Finnish (NFE) AF: 0.0723 AC: 80388 AN: 1111976

Other (OTH) AF: 0.0843 AC: 5089 AN: 60392

GnomAD4 genome AF: 0.158 AC: 24045 AN: 152200 Hom.: 3263 Cov.: 32 AF XY: 0.155 AC XY: 11571 AN XY: 74414

African (AFR) AF: 0.372 AC: 15425 AN: 41492

American (AMR) AF: 0.0953 AC: 1458 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4828

European-Finnish (FIN) AF: 0.107 AC: 1138 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0783 AC: 5324 AN: 68000

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.101 Hom.: 5119

Bravo AF: 0.166

TwinsUK AF: 0.0612 AC: 227

ALSPAC AF: 0.0685 AC: 264

ESP6500AA AF: 0.353 AC: 1552

ESP6500EA AF: 0.0713 AC: 613

ExAC AF: 0.0909 AC: 11039

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.2
DANN	Benign	0.28
DEOGEN2	Benign	0.0090	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.060	T;T
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.10	N;.
PhyloP100		0.70
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.62	N;N
REVEL	Benign	0.044
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.021
MPC		0.16
ClinPred		0.00018	T
GERP RS		2.9
Varity_R		0.053
gMVP		0.21
Mutation Taster		=95/5	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: rs16945874; hg19: chr16-48175235; COSMIC: COSV60914581;