rs45492500

chr16-16090378-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.2461-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,557,780 control chromosomes in the GnomAD database, including 1,907 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 0.036 (134 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1773 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.2461-27G>A		intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.2461-27G>A		intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5482 AN: 152186 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0335

GnomAD3 exomes AF: 0.0379 AC: 7980 AN: 210296 Hom.: 218 AF XY: 0.0393 AC XY: 4420 AN XY: 112402

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.0165

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.0000590

Gnomad SAS exome AF: 0.0159

Gnomad FIN exome AF: 0.0609

Gnomad NFE exome AF: 0.0566

Gnomad OTH exome AF: 0.0396

GnomAD4 exome AF: 0.0480 AC: 67512 AN: 1405476 Hom.: 1773 Cov.: 34 AF XY: 0.0474 AC XY: 32806 AN XY: 691886

Gnomad4 AFR exome AF: 0.00885

Gnomad4 AMR exome AF: 0.0176

Gnomad4 ASJ exome AF: 0.0342

Gnomad4 EAS exome AF: 0.0000777

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.0607

Gnomad4 NFE exome AF: 0.0544

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0360 AC: 5479 AN: 152304 Hom.: 134 Cov.: 32 AF XY: 0.0344 AC XY: 2565 AN XY: 74466

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0505

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.114 Hom.: 965

Bravo AF: 0.0338

Asia WGS AF: 0.00924 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0020
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs45492500; hg19: chr16-16184235;