rs2230671

chr16-16134385-G-Achr16-16134385-G-C

Variant summary

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

The NM_004996.4(ABCC1):c.4002G>A(p.Ser1334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,802 control chromosomes in the GnomAD database, including 57,722 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 0.22 (4412 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53310 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-0.85).
• BP7: Synonymous conserved (PhyloP=-1.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.4002G>A	p.Ser1334=	synonymous_variant	28/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.4002G>A	p.Ser1334=	synonymous_variant	28/31	1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34014 AN: 151846 Hom.: 4410 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.210

GnomAD3 exomes AF: 0.249 AC: 62090 AN: 249422 Hom.: 8450 AF XY: 0.247 AC XY: 33396 AN XY: 135344

Gnomad AFR exome AF: 0.0934

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.115

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.265 AC: 387966 AN: 1461838 Hom.: 53310 Cov.: 38 AF XY: 0.263 AC XY: 190942 AN XY: 727220

Gnomad4 AFR exome AF: 0.0915

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.224 AC: 34022 AN: 151964 Hom.: 4412 Cov.: 32 AF XY: 0.225 AC XY: 16714 AN XY: 74258

Gnomad4 AFR AF: 0.0977

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.208

Alfa AF: 0.265 Hom.: 8183

Bravo AF: 0.213

Asia WGS AF: 0.149 AC: 518 AN: 3478

EpiCase AF: 0.267

EpiControl AF: 0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.43
Dann	Benign	0.66
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: rs2230671; hg19: chr16-16228242; COSMIC: COSV60679240;