rs2283512

chr16-16126345-A-Cchr16-16126345-A-Gchr16-16126345-A-T

Variant summary

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

The NM_004996.4(ABCC1):c.3819+434A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,024 control chromosomes in the GnomAD database, including 28,254 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 0.59 (28254 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.3819+434A>C		intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.3819+434A>C		intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90065 AN: 151906 Hom.: 28257 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.593 AC: 90081 AN: 152024 Hom.: 28254 Cov.: 32 AF XY: 0.594 AC XY: 44141 AN XY: 74304

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.637

Alfa AF: 0.675 Hom.: 30205

Bravo AF: 0.575

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.4
Dann	Benign	0.63

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: rs2283512; hg19: chr16-16220202;