16-16079370-C-T

Position:

• chr16-16079370-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_004996.4(ABCC1):​c.2007C>T​(p.Pro669=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,613,996 control chromosomes in the GnomAD database, including 27 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 0.0011 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (24 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.70

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-3.7 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00114 (174/152286) while in subpopulation EAS AF= 0.0232 (120/5182). AF 95% confidence interval is 0.0198. There are 3 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC1	NM_004996.4	c.2007C>T	p.Pro669=	synonymous_variant	16/31	ENST00000399410.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC1	ENST00000399410.8	c.2007C>T	p.Pro669=	synonymous_variant	16/31	1	NM_004996.4	P1

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 176 AN: 152168 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00222 AC: 554 AN: 249254 Hom.: 5 AF XY: 0.00229 AC XY: 310 AN XY: 135232

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.0242

Gnomad SAS exome AF: 0.00294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.000990

GnomAD4 exome AF: 0.00117 AC: 1713 AN: 1461710 Hom.: 24 Cov.: 30 AF XY: 0.00125 AC XY: 909 AN XY: 727156

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.0318

Gnomad4 SAS exome AF: 0.00279

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.000944

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152286 Hom.: 3 Cov.: 32 AF XY: 0.00134 AC XY: 100 AN XY: 74476

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0232

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00832 Hom.: 708

Bravo AF: 0.00128

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2301666; hg19: chr16-16173227; COSMIC: COSV60680573;