rs2230669

chr16-16044456-G-A

Variant summary

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

The NM_004996.4(ABCC1):c.816G>A(p.Pro272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 1,612,626 control chromosomes in the GnomAD database, including 2,668 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 0.049 (197 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2471 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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=-0.9).
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.816G>A	p.Pro272=	synonymous_variant	8/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.816G>A	p.Pro272=	synonymous_variant	8/31	1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7455 AN: 152190 Hom.: 197 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0409

Gnomad ASJ AF: 0.0504

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0136

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0568

GnomAD3 exomes AF: 0.0427 AC: 10586 AN: 247784 Hom.: 278 AF XY: 0.0422 AC XY: 5679 AN XY: 134572

Gnomad AFR exome AF: 0.0439

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0457

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.0164

Gnomad FIN exome AF: 0.0346

Gnomad NFE exome AF: 0.0603

Gnomad OTH exome AF: 0.0529

GnomAD4 exome AF: 0.0544 AC: 79458 AN: 1460318 Hom.: 2471 Cov.: 31 AF XY: 0.0536 AC XY: 38927 AN XY: 726536

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.0339

Gnomad4 ASJ exome AF: 0.0478

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0167

Gnomad4 FIN exome AF: 0.0359

Gnomad4 NFE exome AF: 0.0613

Gnomad4 OTH exome AF: 0.0544

GnomAD4 genome AF: 0.0490 AC: 7467 AN: 152308 Hom.: 197 Cov.: 32 AF XY: 0.0476 AC XY: 3542 AN XY: 74480

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.0409

Gnomad4 ASJ AF: 0.0504

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0143

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0609

Gnomad4 OTH AF: 0.0562

Alfa AF: 0.0567 Hom.: 334

Bravo AF: 0.0496

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.0616

EpiControl AF: 0.0622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.79
Dann	Benign	0.48
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2230669; hg19: chr16-16138313;