rs4148348

Positions:

• chr16-16068071-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.1678-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,547,218 control chromosomes in the GnomAD database, including 3,497 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 0.057 (338 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3159 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.75

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1678-85G>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.1678-85G>A		intron_variant		1	NM_004996.4	ENSP00000382342	P1

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8727 AN: 152050 Hom.: 337 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0625 AC: 87178 AN: 1395050 Hom.: 3159 AF XY: 0.0628 AC XY: 43488 AN XY: 692330

Gnomad4 AFR exome AF: 0.0106

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.0669

Gnomad4 EAS exome AF: 0.0926

Gnomad4 SAS exome AF: 0.0652

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.0583

Gnomad4 OTH exome AF: 0.0660

GnomAD4 genome AF: 0.0574 AC: 8728 AN: 152168 Hom.: 338 Cov.: 32 AF XY: 0.0635 AC XY: 4722 AN XY: 74376

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0716

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.0697

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.0613

Gnomad4 OTH AF: 0.0606

Alfa AF: 0.0575 Hom.: 150

Bravo AF: 0.0463

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.50

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: rs4148348; hg19: chr16-16161928;