rs35595

Variant names:

• chr16-16056014-G-A
• rs35595
• NM_004996.4:c.1474-78G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-16056014-G-A
• chr16-16056014-G-T

Variant summary

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

The NM_004996.4(ABCC1):​c.1474-78G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,297,882 control chromosomes in the GnomAD database, including 20,742 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 0.23 (5609 hom., cov: 31)
  • Exomes 𝑓: 0.15 (15133 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-1.08).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1474-78G>A		intron_variant	Intron 11 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.1474-78G>A		intron_variant	Intron 11 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35197 AN: 151760 Hom.: 5593 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.152 AC: 174175 AN: 1146004 Hom.: 15133 AF XY: 0.151 AC XY: 86943 AN XY: 576876

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.232 AC: 35253 AN: 151878 Hom.: 5609 Cov.: 31 AF XY: 0.231 AC XY: 17159 AN XY: 74234

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.216

Alfa AF: 0.151 Hom.: 2437

Bravo AF: 0.247

Asia WGS AF: 0.229 AC: 794 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.27
DANN	Benign	0.53

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: rs35595; hg19: chr16-16149871; COSMIC: COSV60691108;