rs246221

chr16-16044465-T-Cchr16-16044465-T-G

Variant summary

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

The NM_004996.4(ABCC1):c.825T>C(p.Val275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,612,872 control chromosomes in the GnomAD database, including 88,479 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 0.41 (14303 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74176 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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=-0.94).
• BP7: Synonymous conserved (PhyloP=-1.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.825T>C	p.Val275=	synonymous_variant	8/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.825T>C	p.Val275=	synonymous_variant	8/31	1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61715 AN: 151988 Hom.: 14273 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.378

GnomAD3 exomes AF: 0.333 AC: 82607 AN: 247936 Hom.: 15165 AF XY: 0.320 AC XY: 43051 AN XY: 134598

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.428

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.305

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.311 AC: 453976 AN: 1460766 Hom.: 74176 Cov.: 37 AF XY: 0.306 AC XY: 222661 AN XY: 726720

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.406 AC: 61794 AN: 152106 Hom.: 14303 Cov.: 32 AF XY: 0.405 AC XY: 30090 AN XY: 74358

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.375

Alfa AF: 0.319 Hom.: 18949

Bravo AF: 0.423

Asia WGS AF: 0.328 AC: 1140 AN: 3478

EpiCase AF: 0.308

EpiControl AF: 0.313

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.31
Dann	Benign	0.49
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs246221; hg19: chr16-16138322;