16-16008018-G-A

Position:

• chr16-16008018-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.225+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 577,782 control chromosomes in the GnomAD database, including 4,122 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 0.051 (237 hom., cov: 29)
  • Exomes 𝑓: 0.19 (3885 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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]

ABCC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.225+26G>A		intron_variant		ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.225+26G>A		intron_variant		1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7213 AN: 141906 Hom.: 237 Cov.: 29

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0486

Gnomad EAS AF: 0.000944

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0587

GnomAD3 exomes AF: 0.0534 AC: 10139 AN: 189756 Hom.: 392 AF XY: 0.0533 AC XY: 5575 AN XY: 104644

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.0435

Gnomad ASJ exome AF: 0.0499

Gnomad EAS exome AF: 0.000170

Gnomad SAS exome AF: 0.0188

Gnomad FIN exome AF: 0.0624

Gnomad NFE exome AF: 0.0734

Gnomad OTH exome AF: 0.0688

GnomAD4 exome AF: 0.189 AC: 82324 AN: 435740 Hom.: 3885 Cov.: 8 AF XY: 0.171 AC XY: 40213 AN XY: 235726

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.0583

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0249

Gnomad4 FIN exome AF: 0.0913

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.0508 AC: 7221 AN: 142042 Hom.: 237 Cov.: 29 AF XY: 0.0509 AC XY: 3499 AN XY: 68798

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.0526

Gnomad4 ASJ AF: 0.0486

Gnomad4 EAS AF: 0.000944

Gnomad4 SAS AF: 0.0188

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0736

Gnomad4 OTH AF: 0.0581

Alfa AF: 0.0607 Hom.: 505

Bravo AF: 0.0452

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.76

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: rs8187843; hg19: chr16-16101875;