16-16068162-T-C

Variant names:

• chr16-16068162-T-C
• rs35605
• NM_004996.4:c.1684T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004996.4(ABCC1):​c.1684T>C​(p.Leu562Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 1,613,856 control chromosomes in the GnomAD database, including 542,071 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 0.83 (52819 hom., cov: 31)
  • Exomes 𝑓: 0.82 (489252 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 39 publications found

Genes affected

ABCC1 (HGNC:51): (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra-and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a multispecific organic anion transporter, with oxidized glutatione, cysteinyl leukotrienes, and activated aflatoxin B1 as substrates. This protein also transports glucuronides and sulfate conjugates of steroid hormones and bile salts. Alternatively spliced variants of this gene have been described but their full-length nature is unknown. [provided by RefSeq, Apr 2012]

ABCC1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 77

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=0.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1684T>C	p.Leu562Leu	synonymous_variant	Exon 13 of 31	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.1684T>C	p.Leu562Leu	synonymous_variant	Exon 13 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126461 AN: 152052 Hom.: 52781 Cov.: 31

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.805

GnomAD2 exomes AF: 0.792 AC: 197671 AN: 249450 AF XY: 0.784

Gnomad AFR exome AF: 0.879

Gnomad AMR exome AF: 0.777

Gnomad ASJ exome AF: 0.767

Gnomad EAS exome AF: 0.791

Gnomad FIN exome AF: 0.839

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.797

GnomAD4 exome AF: 0.816 AC: 1192679 AN: 1461686 Hom.: 489252 Cov.: 63 AF XY: 0.810 AC XY: 588637 AN XY: 727136

African (AFR) AF: 0.874 AC: 29274 AN: 33480

American (AMR) AF: 0.781 AC: 34905 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 20032 AN: 26134

East Asian (EAS) AF: 0.772 AC: 30643 AN: 39698

South Asian (SAS) AF: 0.616 AC: 53126 AN: 86246

European-Finnish (FIN) AF: 0.837 AC: 44643 AN: 53346

Middle Eastern (MID) AF: 0.761 AC: 4390 AN: 5768

European-Non Finnish (NFE) AF: 0.834 AC: 926955 AN: 1111902

Other (OTH) AF: 0.807 AC: 48711 AN: 60392

GnomAD4 genome AF: 0.832 AC: 126547 AN: 152170 Hom.: 52819 Cov.: 31 AF XY: 0.826 AC XY: 61478 AN XY: 74398

African (AFR) AF: 0.878 AC: 36440 AN: 41514

American (AMR) AF: 0.799 AC: 12211 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2693 AN: 3470

East Asian (EAS) AF: 0.796 AC: 4101 AN: 5152

South Asian (SAS) AF: 0.614 AC: 2958 AN: 4820

European-Finnish (FIN) AF: 0.838 AC: 8885 AN: 10604

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56502 AN: 68012

Other (OTH) AF: 0.799 AC: 1690 AN: 2114

Alfa AF: 0.822 Hom.: 134377

Bravo AF: 0.832

Asia WGS AF: 0.718 AC: 2500 AN: 3478

EpiCase AF: 0.821

EpiControl AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.8
DANN	Benign	0.35
PhyloP100		0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs35605; hg19: chr16-16162019; COSMIC: COSV108170128;