NM_004996.4:c.2115+1695A>T

Variant names:

• chr16-16081173-A-T
• rs3887412
• NM_004996.4:c.2115+1695A>T

Variant summary

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

The NM_004996.4(ABCC1):​c.2115+1695A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,114 control chromosomes in the GnomAD database, including 6,011 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 0.25 (6011 hom., cov: 33)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.522
• Publications: 10 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.2115+1695A>T		intron_variant	Intron 16 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.2115+1695A>T		intron_variant	Intron 16 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37423 AN: 151996 Hom.: 5996 Cov.: 33

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.246 AC: 37479 AN: 152114 Hom.: 6011 Cov.: 33 AF XY: 0.242 AC XY: 18029 AN XY: 74366

African (AFR) AF: 0.463 AC: 19190 AN: 41478

American (AMR) AF: 0.159 AC: 2436 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 630 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1151 AN: 5188

South Asian (SAS) AF: 0.128 AC: 620 AN: 4826

European-Finnish (FIN) AF: 0.131 AC: 1388 AN: 10584

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11379 AN: 67974

Other (OTH) AF: 0.212 AC: 448 AN: 2112

Alfa AF: 0.206 Hom.: 503

Bravo AF: 0.258

Asia WGS AF: 0.218 AC: 760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.56
PhyloP100		0.52
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: rs3887412; hg19: chr16-16175030;