rs16945869

Positions:

• chr16-48140648-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393797.1(ABCC12):​c.657+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 1,586,518 control chromosomes in the GnomAD database, including 9,392 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 0.16 (3257 hom., cov: 32)
  • Exomes 𝑓: 0.076 (6135 hom.)
• Consequence: ABCC12 NM_001393797.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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/exons	MANE	Protein	UniProt
ABCC12	NM_001393797.1	c.657+39C>T		intron_variant		ENST00000311303.8	NP_001380726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC12	ENST00000311303.8	c.657+39C>T		intron_variant		1	NM_001393797.1	ENSP00000311030.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23936 AN: 151856 Hom.: 3242 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.0842 AC: 20663 AN: 245300 Hom.: 1697 AF XY: 0.0788 AC XY: 10473 AN XY: 132906

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.0525

Gnomad ASJ exome AF: 0.0588

Gnomad EAS exome AF: 0.000219

Gnomad SAS exome AF: 0.0269

Gnomad FIN exome AF: 0.109

Gnomad NFE exome AF: 0.0800

Gnomad OTH exome AF: 0.0750

GnomAD4 exome AF: 0.0757 AC: 108644 AN: 1434544 Hom.: 6135 Cov.: 28 AF XY: 0.0738 AC XY: 52709 AN XY: 713880

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.0564

Gnomad4 ASJ exome AF: 0.0591

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.0276

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0723

Gnomad4 OTH exome AF: 0.0843

GnomAD4 genome AF: 0.158 AC: 23991 AN: 151974 Hom.: 3257 Cov.: 32 AF XY: 0.155 AC XY: 11534 AN XY: 74294

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.0949

Gnomad4 ASJ AF: 0.0562

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0784

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0944 Hom.: 1113

Bravo AF: 0.166

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
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.036
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs16945869; hg19: chr16-48174559;