rs212087

Positions:

• chr16-16136433-G-A

Variant summary

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

The NM_004996.4(ABCC1):​c.4126-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 1,601,180 control chromosomes in the GnomAD database, including 133,964 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 0.36 (10650 hom., cov: 31)
  • Exomes 𝑓: 0.41 (123314 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.4126-45G>A		intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.4126-45G>A		intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54190 AN: 151832 Hom.: 10645 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.388 AC: 92966 AN: 239692 Hom.: 18814 AF XY: 0.393 AC XY: 51097 AN XY: 130086

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.423

Gnomad EAS exome AF: 0.231

Gnomad SAS exome AF: 0.369

Gnomad FIN exome AF: 0.437

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.409 AC: 593200 AN: 1449230 Hom.: 123314 Cov.: 32 AF XY: 0.409 AC XY: 294279 AN XY: 719266

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.357 AC: 54216 AN: 151950 Hom.: 10650 Cov.: 31 AF XY: 0.358 AC XY: 26610 AN XY: 74272

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.372

Alfa AF: 0.417 Hom.: 15147

Bravo AF: 0.342

Asia WGS AF: 0.365 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.57

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: rs212087; hg19: chr16-16230290; COSMIC: COSV60686191;