rs212090

Variant names:

• chr16-16142147-T-A
• rs212090
• NM_004996.4:c.*866T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004996.4(ABCC1):​c.*866T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,652 control chromosomes in the GnomAD database, including 11,079 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 0.36 (11079 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCC1 NM_004996.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 33 publications found

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]

ABCC1 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 77

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.*866T>A		3_prime_UTR_variant	Exon 31 of 31	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.*866T>A		3_prime_UTR_variant	Exon 31 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54649 AN: 151534 Hom.: 11077 Cov.: 30

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.378

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.360 AC: 54659 AN: 151652 Hom.: 11079 Cov.: 30 AF XY: 0.361 AC XY: 26731 AN XY: 74060

African (AFR) AF: 0.179 AC: 7419 AN: 41366

American (AMR) AF: 0.429 AC: 6526 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3468

East Asian (EAS) AF: 0.175 AC: 894 AN: 5122

South Asian (SAS) AF: 0.339 AC: 1621 AN: 4776

European-Finnish (FIN) AF: 0.460 AC: 4833 AN: 10498

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30492 AN: 67892

Other (OTH) AF: 0.374 AC: 786 AN: 2102

Alfa AF: 0.419 Hom.: 8006

Bravo AF: 0.345

Asia WGS AF: 0.265 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs212090; hg19: chr16-16236004;