16-15992809-C-G

Variant names:

• chr16-15992809-C-G
• rs152022
• NM_004996.4:c.49-15007C>G

Variant summary

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

The NM_004996.4(ABCC1):​c.49-15007C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,068 control chromosomes in the GnomAD database, including 41,302 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 0.73 (41302 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 4 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):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 77

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004996.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.49-15007C>G		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.49-15007C>G		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.49-15007C>G		intron	N/A	NP_063957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.49-15007C>G		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.49-15007C>G		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000574224.2	TSL:1	n.124-15007C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111330 AN: 151950 Hom.: 41279 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.733 AC: 111399 AN: 152068 Hom.: 41302 Cov.: 32 AF XY: 0.728 AC XY: 54128 AN XY: 74336

African (AFR) AF: 0.621 AC: 25736 AN: 41472

American (AMR) AF: 0.717 AC: 10960 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 2781 AN: 3468

East Asian (EAS) AF: 0.712 AC: 3674 AN: 5160

South Asian (SAS) AF: 0.793 AC: 3827 AN: 4826

European-Finnish (FIN) AF: 0.705 AC: 7448 AN: 10562

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54603 AN: 67988

Other (OTH) AF: 0.760 AC: 1602 AN: 2108

Alfa AF: 0.719 Hom.: 2273

Bravo AF: 0.725

Asia WGS AF: 0.728 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.63
DANN	Benign	0.35
PhyloP100		-1.3
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: rs152022; hg19: chr16-16086666;