chr16-48140648-G-A

Variant names:

• chr16-48140648-G-A
• rs16945869
• NM_001393797.1:c.657+39C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393797.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	NM_001393797.1	MANE Select	c.657+39C>T		intron	N/A	NP_001380726.1
	ABCC12	NM_033226.3		c.657+39C>T		intron	N/A	NP_150229.2
	ABCC12	NM_001392028.1		c.657+39C>T		intron	N/A	NP_001378957.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	ENST00000311303.8	TSL:1 MANE Select	c.657+39C>T		intron	N/A	ENSP00000311030.4
	ABCC12	ENST00000497206.6	TSL:1	n.657+39C>T		intron	N/A	ENSP00000431232.1
	ABCC12	ENST00000529084.5	TSL:1	n.657+39C>T		intron	N/A	ENSP00000434510.1

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

GnomAD2 exomes AF: 0.0842 AC: 20663 AN: 245300 AF XY: 0.0788

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 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

African (AFR) AF: 0.374 AC: 12243 AN: 32758

American (AMR) AF: 0.0564 AC: 2481 AN: 44020

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 1516 AN: 25630

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39482

South Asian (SAS) AF: 0.0276 AC: 2332 AN: 84466

European-Finnish (FIN) AF: 0.108 AC: 5702 AN: 53018

Middle Eastern (MID) AF: 0.0957 AC: 545 AN: 5692

European-Non Finnish (NFE) AF: 0.0723 AC: 78815 AN: 1090132

Other (OTH) AF: 0.0843 AC: 5004 AN: 59346

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

African (AFR) AF: 0.372 AC: 15387 AN: 41348

American (AMR) AF: 0.0949 AC: 1448 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4814

European-Finnish (FIN) AF: 0.107 AC: 1133 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0784 AC: 5328 AN: 67994

Other (OTH) AF: 0.120 AC: 252 AN: 2106

Alfa AF: 0.110 Hom.: 2330

Bravo AF: 0.166

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.036
DANN	Benign	0.38
PhyloP100		-0.99
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: rs16945869; hg19: chr16-48174559;