16-16142082-G-C

Variant names:

• chr16-16142082-G-C
• rs129081
• NM_004996.4:c.*801G>C

Variant summary

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

The NM_004996.4(ABCC1):​c.*801G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 134,262 control chromosomes in the GnomAD database, including 14,829 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 0.49 (14829 hom., cov: 26)
  • Exomes 𝑓: 0.50 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: ABCC1 NM_004996.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.26
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.*801G>C		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.*801G>C		3_prime_UTR_variant	Exon 31 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 65883 AN: 134144 Hom.: 14807 Cov.: 26

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.486

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.500 AC: 2 AN: 4 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

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) AF: 1.00 AC: 2 AN: 2

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: 0.491 AC: 65953 AN: 134262 Hom.: 14829 Cov.: 26 AF XY: 0.503 AC XY: 32575 AN XY: 64728

African (AFR) AF: 0.553 AC: 20616 AN: 37260

American (AMR) AF: 0.469 AC: 5933 AN: 12638

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1160 AN: 3070

East Asian (EAS) AF: 0.717 AC: 3424 AN: 4774

South Asian (SAS) AF: 0.608 AC: 2674 AN: 4398

European-Finnish (FIN) AF: 0.528 AC: 4249 AN: 8040

Middle Eastern (MID) AF: 0.481 AC: 130 AN: 270

European-Non Finnish (NFE) AF: 0.435 AC: 26677 AN: 61284

Other (OTH) AF: 0.485 AC: 880 AN: 1816

Alfa AF: 0.412 Hom.: 7490

Bravo AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.65
PhyloP100		-5.3
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: rs129081; hg19: chr16-16235939;