rs8187858

chr16-16068182-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004996.4(ABCC1):c.1704C>T(p.Tyr568=) 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ABCC1	NM_004996.4	c.1704C>T	p.Tyr568=	synonymous_variant	13/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.1704C>T	p.Tyr568=	synonymous_variant	13/31	1	NM_004996.4	P1

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

GnomAD3 exomes AF: 0.0669 AC: 16687 AN: 249534 Hom.: 706 AF XY: 0.0675 AC XY: 9137 AN XY: 135378

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 SAS exome AF: 0.0356

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

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.0468

Gnomad4 ASJ exome AF: 0.0853

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0368

Gnomad4 FIN exome AF: 0.0664

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0867

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

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.0625

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0326

Gnomad4 FIN AF: 0.0646

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0883 Hom.: 1135

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs8187858; hg19: chr16-16162039;