rs16945894

Variant names:

• chr16-48146199-C-T
• rs16945894
• NM_001393797.1:c.119+107G>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.119+107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 966,502 control chromosomes in the GnomAD database, including 3,713 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 0.068 (459 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3254 hom.)
• Consequence: ABCC12 NM_001393797.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 8 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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC12	NM_001393797.1	c.119+107G>A		intron_variant	Intron 3 of 30	ENST00000311303.8	NP_001380726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC12	ENST00000311303.8	c.119+107G>A		intron_variant	Intron 3 of 30	1	NM_001393797.1	ENSP00000311030.4

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10406 AN: 152114 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0603

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.0839

Gnomad SAS AF: 0.0304

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.0772

GnomAD4 exome AF: 0.0845 AC: 68842 AN: 814270 Hom.: 3254 AF XY: 0.0828 AC XY: 34929 AN XY: 422086

African (AFR) AF: 0.0160 AC: 324 AN: 20282

American (AMR) AF: 0.0465 AC: 1736 AN: 37328

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 1169 AN: 18588

East Asian (EAS) AF: 0.0854 AC: 3114 AN: 36448

South Asian (SAS) AF: 0.0281 AC: 1811 AN: 64548

European-Finnish (FIN) AF: 0.108 AC: 5374 AN: 49872

Middle Eastern (MID) AF: 0.0680 AC: 275 AN: 4044

European-Non Finnish (NFE) AF: 0.0953 AC: 51928 AN: 544606

Other (OTH) AF: 0.0807 AC: 3111 AN: 38554

GnomAD4 genome AF: 0.0683 AC: 10398 AN: 152232 Hom.: 459 Cov.: 32 AF XY: 0.0673 AC XY: 5013 AN XY: 74456

African (AFR) AF: 0.0177 AC: 736 AN: 41552

American (AMR) AF: 0.0601 AC: 919 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0606 AC: 210 AN: 3468

East Asian (EAS) AF: 0.0841 AC: 435 AN: 5170

South Asian (SAS) AF: 0.0300 AC: 145 AN: 4826

European-Finnish (FIN) AF: 0.104 AC: 1105 AN: 10610

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6553 AN: 68006

Other (OTH) AF: 0.0759 AC: 160 AN: 2108

Alfa AF: 0.0815 Hom.: 1165

Bravo AF: 0.0635

Asia WGS AF: 0.0530 AC: 185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.73
PhyloP100		0.093
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: rs16945894; hg19: chr16-48180110;