rs4148337

Positions:

• chr16-16014425-T-C

Variant summary

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

The NM_004996.4(ABCC1):​c.352-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,563,264 control chromosomes in the GnomAD database, including 353,318 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.64 (31669 hom., cov: 32)
  • Exomes 𝑓: 0.67 (321649 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.352-66T>C		intron_variant		ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.352-66T>C		intron_variant		1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97233 AN: 151896 Hom.: 31661 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.638

GnomAD4 exome AF: 0.670 AC: 945329 AN: 1411250 Hom.: 321649 AF XY: 0.666 AC XY: 465009 AN XY: 698418

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.652

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.704

Gnomad4 OTH exome AF: 0.652

GnomAD4 genome AF: 0.640 AC: 97272 AN: 152014 Hom.: 31669 Cov.: 32 AF XY: 0.630 AC XY: 46800 AN XY: 74294

Gnomad4 AFR AF: 0.593

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.632

Alfa AF: 0.673 Hom.: 4303

Bravo AF: 0.635

Asia WGS AF: 0.416 AC: 1452 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	0.11
DANN	Benign	0.69
BranchPoint Hunter		0.0

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: rs4148337; hg19: chr16-16108282; COSMIC: COSV60682511; COSMIC: COSV60682511;