NM_004996.4:c.352-196A>C

Variant names:

• chr16-16014295-A-C
• rs4148336
• NM_004996.4:c.352-196A>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.352-196A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,032 control chromosomes in the GnomAD database, including 6,180 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 (6180 hom., cov: 33)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.352-196A>C		intron_variant	Intron 3 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.352-196A>C		intron_variant	Intron 3 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37537 AN: 151914 Hom.: 6167 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0413

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.247 AC: 37581 AN: 152032 Hom.: 6180 Cov.: 33 AF XY: 0.240 AC XY: 17830 AN XY: 74314

African (AFR) AF: 0.464 AC: 19220 AN: 41426

American (AMR) AF: 0.155 AC: 2371 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.0414 AC: 214 AN: 5174

South Asian (SAS) AF: 0.135 AC: 651 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1282 AN: 10584

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.181 AC: 12305 AN: 67976

Other (OTH) AF: 0.244 AC: 513 AN: 2106

Alfa AF: 0.220 Hom.: 549

Bravo AF: 0.257

Asia WGS AF: 0.122 AC: 426 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	5.1
DANN	Benign	0.76
PhyloP100		0.68
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: rs4148336; hg19: chr16-16108152;