rs61733849

Variant names:

• chr16-48083763-C-T
• rs61733849
• NM_001393797.1:c.4032G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001393797.1(ABCC12):​c.4032G>A​(p.Lys1344Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,614,204 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00077 (9 hom.)
• Consequence: ABCC12 NM_001393797.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.296
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 16-48083763-C-T is Benign according to our data. Variant chr16-48083763-C-T is described in ClinVar as Benign. ClinVar VariationId is 720010.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.296 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00807 (1229/152334) while in subpopulation AFR AF = 0.0286 (1189/41562). AF 95% confidence interval is 0.0273. There are 18 homozygotes in GnomAd4. There are 569 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	NM_001393797.1	MANE Select	c.4032G>A	p.Lys1344Lys	synonymous	Exon 31 of 31	NP_001380726.1
	ABCC12	NM_033226.3		c.4032G>A	p.Lys1344Lys	synonymous	Exon 31 of 31	NP_150229.2	Q96J65-1
	ABCC12	NM_001393799.1		c.654G>A	p.Lys218Lys	synonymous	Exon 7 of 7	NP_001380728.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC12	ENST00000311303.8	TSL:1 MANE Select	c.4032G>A	p.Lys1344Lys	synonymous	Exon 31 of 31	ENSP00000311030.4
	ABCC12	ENST00000497206.6	TSL:1	n.*944G>A		non_coding_transcript_exon	Exon 28 of 28	ENSP00000431232.1	Q96J65-2
	ABCC12	ENST00000529084.5	TSL:1	n.*1999G>A		non_coding_transcript_exon	Exon 29 of 29	ENSP00000434510.1	Q96J65-4

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 1230 AN: 152216 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00205 AC: 516 AN: 251228 AF XY: 0.00141

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000772 AC: 1128 AN: 1461870 Hom.: 9 Cov.: 31 AF XY: 0.000660 AC XY: 480 AN XY: 727238

African (AFR) AF: 0.0294 AC: 983 AN: 33472

American (AMR) AF: 0.00101 AC: 45 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1112008

Other (OTH) AF: 0.00139 AC: 84 AN: 60394

GnomAD4 genome AF: 0.00807 AC: 1229 AN: 152334 Hom.: 18 Cov.: 33 AF XY: 0.00764 AC XY: 569 AN XY: 74496

African (AFR) AF: 0.0286 AC: 1189 AN: 41562

American (AMR) AF: 0.00176 AC: 27 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00354 Hom.: 14

Bravo AF: 0.00888

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		0.30
Mutation Taster		=96/4	polymorphism

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: rs61733849; hg19: chr16-48117674;