rs35587

chr16-16045857-T-Cchr16-16045857-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.1062T>C(p.Asn354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,613,574 control chromosomes in the GnomAD database, including 87,235 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 0.40 (14193 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73042 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88

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=-0.87).
• BP7: Synonymous conserved (PhyloP=-3.88 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.1062T>C	p.Asn354=	synonymous_variant	9/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.1062T>C	p.Asn354=	synonymous_variant	9/31	1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61352 AN: 151940 Hom.: 14162 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.375

GnomAD3 exomes AF: 0.331 AC: 82189 AN: 248262 Hom.: 14976 AF XY: 0.318 AC XY: 42826 AN XY: 134698

Gnomad AFR exome AF: 0.656

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.428

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.302

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.308 AC: 450630 AN: 1461516 Hom.: 73042 Cov.: 41 AF XY: 0.304 AC XY: 221058 AN XY: 727058

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.415

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.341

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.404 AC: 61434 AN: 152058 Hom.: 14193 Cov.: 32 AF XY: 0.402 AC XY: 29910 AN XY: 74326

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.372

Alfa AF: 0.310 Hom.: 17830

Bravo AF: 0.421

Asia WGS AF: 0.329 AC: 1145 AN: 3478

EpiCase AF: 0.305

EpiControl AF: 0.310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.024
Dann	Benign	0.37

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: rs35587; hg19: chr16-16139714; COSMIC: COSV60680042;