rs16967755

chr16-16105398-A-Gchr16-16105398-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.2736-1340A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,094 control chromosomes in the GnomAD database, including 6,337 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 0.28 (6334 hom., cov: 32)
  • Exomes 𝑓: 0.28 (3 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Scores: Splicing: ADA: 0.00002453
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.2736-1340A>G		intron_variant		ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.2736-1340A>G		intron_variant		1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42783 AN: 151894 Hom.: 6322 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.210 AC: 13 AN: 62 Hom.: 1 AF XY: 0.208 AC XY: 5 AN XY: 24

Gnomad AFR exome AF: 0.500

Gnomad FIN exome AF: 0.286

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.280 AC: 23 AN: 82 Hom.: 3 Cov.: 0 AF XY: 0.306 AC XY: 19 AN XY: 62

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.282 AC: 42835 AN: 152012 Hom.: 6334 Cov.: 32 AF XY: 0.285 AC XY: 21141 AN XY: 74292

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.275

Alfa AF: 0.251 Hom.: 787

Bravo AF: 0.281

Asia WGS AF: 0.344 AC: 1197 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	9.0
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0020
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: rs16967755; hg19: chr16-16199255;