16-48087989-T-G

Position:

• chr16-48087989-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001393797.1(ABCC12):​c.3572A>C​(p.Glu1191Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,614,216 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (69 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (73 hom.)
• Consequence: ABCC12 NM_001393797.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.80

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]

ABCC12 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003813982).
• BP6: Variant 16-48087989-T-G is Benign according to our data. Variant chr16-48087989-T-G is described in ClinVar as [Benign]. Clinvar id is 781322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC12	NM_001393797.1	c.3572A>C	p.Glu1191Ala	missense_variant	27/31	ENST00000311303.8	NP_001380726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC12	ENST00000311303.8	c.3572A>C	p.Glu1191Ala	missense_variant	27/31	1	NM_001393797.1	ENSP00000311030.4

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2552 AN: 152240 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00434 AC: 1090 AN: 251134 Hom.: 27 AF XY: 0.00321 AC XY: 435 AN XY: 135712

Gnomad AFR exome AF: 0.0554

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000423

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00187 AC: 2733 AN: 1461858 Hom.: 73 Cov.: 31 AF XY: 0.00168 AC XY: 1220 AN XY: 727230

Gnomad4 AFR exome AF: 0.0592

Gnomad4 AMR exome AF: 0.00315

Gnomad4 ASJ exome AF: 0.000803

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000568

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000217

Gnomad4 OTH exome AF: 0.00404

GnomAD4 genome AF: 0.0168 AC: 2564 AN: 152358 Hom.: 69 Cov.: 32 AF XY: 0.0166 AC XY: 1237 AN XY: 74502

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00336 Hom.: 31

Bravo AF: 0.0189

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0552 AC: 243

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00528 AC: 641

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.73	N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.27
Sift	Benign	0.37	T
Sift4G	Benign	0.30	T
Polyphen		0.051	B
Vest4		0.31
MVP		0.83
MPC		0.20
ClinPred		0.025	T
GERP RS		3.6
Varity_R		0.23
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16945787; hg19: chr16-48121900;