rs3765129

Positions:

• chr16-16056044-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.1474-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,545,676 control chromosomes in the GnomAD database, including 16,013 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 0.11 (1299 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14714 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.1474-48C>T		intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.1474-48C>T		intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17440 AN: 152040 Hom.: 1299 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.134 AC: 32689 AN: 244506 Hom.: 2538 AF XY: 0.129 AC XY: 17180 AN XY: 132684

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.0938

Gnomad EAS exome AF: 0.0962

Gnomad SAS exome AF: 0.0521

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.140 AC: 195211 AN: 1393518 Hom.: 14714 Cov.: 24 AF XY: 0.138 AC XY: 95441 AN XY: 693986

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.0949

Gnomad4 EAS exome AF: 0.0988

Gnomad4 SAS exome AF: 0.0537

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.115 AC: 17439 AN: 152158 Hom.: 1299 Cov.: 32 AF XY: 0.116 AC XY: 8628 AN XY: 74368

Gnomad4 AFR AF: 0.0276

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.0951

Gnomad4 SAS AF: 0.0436

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.113

Alfa AF: 0.138 Hom.: 1576

Bravo AF: 0.109

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3765129; hg19: chr16-16149901; COSMIC: COSV60686572;