NM_004996.4:c.2460+1108T>C

Variant names:

• chr16-16088099-T-C
• rs2889517
• NM_004996.4:c.2460+1108T>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.2460+1108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,856 control chromosomes in the GnomAD database, including 31,469 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 0.64 (31469 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 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.2460+1108T>C		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.2334+1108T>C		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.2313+1108T>C		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.2460+1108T>C		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.2283+1108T>C		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000914156.1		c.2616+1108T>C		intron	N/A	ENSP00000584215.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97240 AN: 151738 Hom.: 31466 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.641 AC: 97279 AN: 151856 Hom.: 31469 Cov.: 32 AF XY: 0.632 AC XY: 46936 AN XY: 74222

African (AFR) AF: 0.576 AC: 23816 AN: 41352

American (AMR) AF: 0.605 AC: 9214 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1987 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3498 AN: 5178

South Asian (SAS) AF: 0.466 AC: 2243 AN: 4810

European-Finnish (FIN) AF: 0.643 AC: 6779 AN: 10540

Middle Eastern (MID) AF: 0.510 AC: 149 AN: 292

European-Non Finnish (NFE) AF: 0.701 AC: 47681 AN: 67980

Other (OTH) AF: 0.605 AC: 1273 AN: 2104

Alfa AF: 0.673 Hom.: 90457

Bravo AF: 0.637

Asia WGS AF: 0.544 AC: 1889 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.31
PhyloP100		-0.20
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: rs2889517; hg19: chr16-16181956;