chr16-48088671-G-A

Variant names:

• chr16-48088671-G-A
• rs7193955
• NM_001393797.1:c.3349C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 34 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=3.6479676E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393799.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	NM_001393797.1	MANE Select	c.3349C>T	p.Arg1117Cys	missense	Exon 26 of 31	NP_001380726.1
	ABCC12	NM_001393799.1		c.-30C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001380728.1
	ABCC12	NM_001393798.1		c.-30C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001380727.1	A0A8I5KPE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	ENST00000311303.8	TSL:1 MANE Select	c.3349C>T	p.Arg1117Cys	missense	Exon 26 of 31	ENSP00000311030.4
	ABCC12	ENST00000497206.6	TSL:1	n.*340C>T		non_coding_transcript_exon	Exon 24 of 28	ENSP00000431232.1	Q96J65-2
	ABCC12	ENST00000526251.1	TSL:1	n.183C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93701 AN: 152052 Hom.: 33866 Cov.: 33

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

GnomAD2 exomes AF: 0.722 AC: 181460 AN: 251320 AF XY: 0.743

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 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.: 57 AF XY: 0.769 AC XY: 558851 AN XY: 727176

African (AFR) AF: 0.191 AC: 6382 AN: 33476

American (AMR) AF: 0.541 AC: 24188 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 20689 AN: 26134

East Asian (EAS) AF: 0.916 AC: 36348 AN: 39698

South Asian (SAS) AF: 0.807 AC: 69612 AN: 86250

European-Finnish (FIN) AF: 0.838 AC: 44758 AN: 53416

Middle Eastern (MID) AF: 0.763 AC: 4398 AN: 5766

European-Non Finnish (NFE) AF: 0.779 AC: 866134 AN: 1111914

Other (OTH) AF: 0.747 AC: 45087 AN: 60390

GnomAD4 genome AF: 0.616 AC: 93696 AN: 152170 Hom.: 33860 Cov.: 33 AF XY: 0.623 AC XY: 46369 AN XY: 74404

African (AFR) AF: 0.209 AC: 8666 AN: 41490

American (AMR) AF: 0.630 AC: 9639 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2742 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4628 AN: 5174

South Asian (SAS) AF: 0.803 AC: 3873 AN: 4822

European-Finnish (FIN) AF: 0.840 AC: 8905 AN: 10602

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52873 AN: 68002

Other (OTH) AF: 0.642 AC: 1358 AN: 2114

Alfa AF: 0.722 Hom.: 110077

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000037	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.15
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.14
Sift	Benign	0.032	D
Sift4G	Uncertain	0.054	T
Polyphen		0.0040	B
Vest4		0.032
MPC		0.19
ClinPred		0.023	T
GERP RS		2.7
Varity_R		0.10
gMVP		0.57
Mutation Taster		=98/2	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: rs7193955; hg19: chr16-48122582; COSMIC: COSV107324328; COSMIC: COSV107324328;