rs3743527

Positions:

• chr16-16141824-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004996.4(ABCC1):​c.*543C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 154,262 control chromosomes in the GnomAD database, including 4,053 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 0.21 (3996 hom., cov: 32)
  • Exomes 𝑓: 0.21 (57 hom.)
• Consequence: ABCC1 NM_004996.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.*543C>T		3_prime_UTR_variant	31/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.*543C>T		3_prime_UTR_variant	31/31	1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32665 AN: 151918 Hom.: 3999 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.212 AC: 471 AN: 2224 Hom.: 57 Cov.: 0 AF XY: 0.202 AC XY: 234 AN XY: 1160

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.215 AC: 32678 AN: 152038 Hom.: 3996 Cov.: 32 AF XY: 0.224 AC XY: 16651 AN XY: 74316

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.199

Alfa AF: 0.212 Hom.: 5981

Bravo AF: 0.204

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.55
DANN	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3743527; hg19: chr16-16235681;