16-16047966-T-C

Variant names:

• chr16-16047966-T-C
• rs35592
• NM_004996.4:c.1219-176T>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.1219-176T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,728 control chromosomes in the GnomAD database, including 9,145 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 0.33 (9145 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.95
• Publications: 24 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 = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1219-176T>C		intron_variant	Intron 9 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.1219-176T>C		intron_variant	Intron 9 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49684 AN: 151610 Hom.: 9138 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.328 AC: 49737 AN: 151728 Hom.: 9145 Cov.: 32 AF XY: 0.329 AC XY: 24389 AN XY: 74160

African (AFR) AF: 0.504 AC: 20840 AN: 41324

American (AMR) AF: 0.287 AC: 4368 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 927 AN: 3464

East Asian (EAS) AF: 0.429 AC: 2203 AN: 5136

South Asian (SAS) AF: 0.185 AC: 893 AN: 4820

European-Finnish (FIN) AF: 0.304 AC: 3196 AN: 10526

Middle Eastern (MID) AF: 0.240 AC: 70 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16199 AN: 67910

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.285 Hom.: 11927

Bravo AF: 0.340

Asia WGS AF: 0.313 AC: 1089 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	0.14
DANN	Benign	0.59
PhyloP100		-3.9
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: rs35592; hg19: chr16-16141823;