rs35604

chr16-16068119-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.1678-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 1,611,314 control chromosomes in the GnomAD database, including 540,370 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 0.83 (52447 hom., cov: 32)
  • Exomes 𝑓: 0.82 (487923 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.03

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.1678-37G>A		intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.1678-37G>A		intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 126030 AN: 152054 Hom.: 52411 Cov.: 32

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.803

GnomAD3 exomes AF: 0.791 AC: 195821 AN: 247594 Hom.: 78261 AF XY: 0.783 AC XY: 105166 AN XY: 134374

Gnomad AFR exome AF: 0.870

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.767

Gnomad EAS exome AF: 0.790

Gnomad SAS exome AF: 0.612

Gnomad FIN exome AF: 0.838

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.796

GnomAD4 exome AF: 0.816 AC: 1189938 AN: 1459142 Hom.: 487923 Cov.: 41 AF XY: 0.809 AC XY: 587212 AN XY: 725826

Gnomad4 AFR exome AF: 0.865

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.766

Gnomad4 EAS exome AF: 0.771

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.836

Gnomad4 NFE exome AF: 0.834

Gnomad4 OTH exome AF: 0.806

GnomAD4 genome AF: 0.829 AC: 126113 AN: 152172 Hom.: 52447 Cov.: 32 AF XY: 0.823 AC XY: 61239 AN XY: 74394

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.797

Alfa AF: 0.814 Hom.: 53385

Bravo AF: 0.829

Asia WGS AF: 0.715 AC: 2489 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	0.024
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs35604; hg19: chr16-16161976;