chr16-16111592-G-A

Variant names:

• chr16-16111592-G-A
• rs3851716
• NM_004996.4:c.3079+10G>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.3079+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,610,546 control chromosomes in the GnomAD database, including 789,687 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 0.94 (68200 hom., cov: 31)
  • Exomes 𝑓: 0.99 (721487 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.3079+10G>A		intron_variant	Intron 22 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.3079+10G>A		intron_variant	Intron 22 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143366 AN: 152112 Hom.: 68153 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.962

GnomAD2 exomes AF: 0.986 AC: 240389 AN: 243922 AF XY: 0.989

Gnomad AFR exome AF: 0.794

Gnomad AMR exome AF: 0.990

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.995

GnomAD4 exome AF: 0.994 AC: 1449938 AN: 1458316 Hom.: 721487 Cov.: 40 AF XY: 0.995 AC XY: 721849 AN XY: 725442

African (AFR) AF: 0.798 AC: 26652 AN: 33400

American (AMR) AF: 0.989 AC: 43751 AN: 44230

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26086 AN: 26088

East Asian (EAS) AF: 1.00 AC: 39672 AN: 39672

South Asian (SAS) AF: 1.00 AC: 85885 AN: 85928

European-Finnish (FIN) AF: 1.00 AC: 53302 AN: 53302

Middle Eastern (MID) AF: 0.990 AC: 4502 AN: 4548

European-Non Finnish (NFE) AF: 1.00 AC: 1110695 AN: 1110962

Other (OTH) AF: 0.987 AC: 59393 AN: 60186

GnomAD4 genome AF: 0.942 AC: 143470 AN: 152230 Hom.: 68200 Cov.: 31 AF XY: 0.944 AC XY: 70304 AN XY: 74440

African (AFR) AF: 0.799 AC: 33153 AN: 41484

American (AMR) AF: 0.980 AC: 14995 AN: 15300

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5180 AN: 5180

South Asian (SAS) AF: 1.00 AC: 4828 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10615 AN: 10616

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67997 AN: 68036

Other (OTH) AF: 0.962 AC: 2026 AN: 2106

Alfa AF: 0.952 Hom.: 21571

Bravo AF: 0.934

Asia WGS AF: 0.989 AC: 3440 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	0.0070
DANN	Benign	0.53
PhyloP100		-0.98
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: rs3851716; hg19: chr16-16205449;