rs8187858

Variant names:

• chr16-16068182-C-T
• rs8187858
• NM_004996.4:c.1704C>T

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.1704C>T​(p.Tyr568Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 1,614,076 control chromosomes in the GnomAD database, including 7,117 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 0.066 (462 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6655 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• Publications: 30 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=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.807 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1704C>T	p.Tyr568Tyr	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.1704C>T	p.Tyr568Tyr	synonymous_variant	Exon 13 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.0662 AC: 10070 AN: 152150 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0708

GnomAD2 exomes AF: 0.0669 AC: 16687 AN: 249534 AF XY: 0.0675

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.0452

Gnomad ASJ exome AF: 0.0846

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.0650

Gnomad NFE exome AF: 0.0976

Gnomad OTH exome AF: 0.0828

GnomAD4 exome AF: 0.0906 AC: 132453 AN: 1461808 Hom.: 6655 Cov.: 36 AF XY: 0.0893 AC XY: 64957 AN XY: 727206

African (AFR) AF: 0.0151 AC: 506 AN: 33480

American (AMR) AF: 0.0468 AC: 2092 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0853 AC: 2230 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0368 AC: 3178 AN: 86258

European-Finnish (FIN) AF: 0.0664 AC: 3547 AN: 53394

Middle Eastern (MID) AF: 0.0579 AC: 334 AN: 5768

European-Non Finnish (NFE) AF: 0.104 AC: 115319 AN: 1111954

Other (OTH) AF: 0.0867 AC: 5237 AN: 60396

GnomAD4 genome AF: 0.0661 AC: 10067 AN: 152268 Hom.: 462 Cov.: 32 AF XY: 0.0635 AC XY: 4728 AN XY: 74452

African (AFR) AF: 0.0183 AC: 762 AN: 41570

American (AMR) AF: 0.0625 AC: 955 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0326 AC: 157 AN: 4820

European-Finnish (FIN) AF: 0.0646 AC: 685 AN: 10606

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6919 AN: 68016

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0846 Hom.: 1765

Bravo AF: 0.0637

Asia WGS AF: 0.0160 AC: 57 AN: 3478

EpiCase AF: 0.0992

EpiControl AF: 0.0968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.0
DANN	Benign	0.32
PhyloP100		-0.81
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: rs8187858; hg19: chr16-16162039;