ENST00000574224.2:n.1808C>T

Variant names:

• chr16-16056351-C-T
• rs17265551
• ENST00000574224.2:n.1808C>T

Variant summary

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

The ENST00000574224.2(ABCC1):​n.1808C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 1,579,524 control chromosomes in the GnomAD database, including 5,820 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 0.074 (457 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5363 hom.)
• Consequence: ABCC1 ENST00000574224.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000574224.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.1677+56C>T		intron	N/A	NP_004987.2
	ABCC1	NM_019901.2		c.1551+56C>T		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.1677+56C>T		intron	N/A	NP_063957.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000574224.2	TSL:1	n.1808C>T		non_coding_transcript_exon	Exon 12 of 12
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.1677+56C>T		intron	N/A	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.1677+56C>T		intron	N/A	ENSP00000461615.2

Frequencies

GnomAD3 genomes AF: 0.0743 AC: 11293 AN: 152042 Hom.: 456 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0658

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0379

Gnomad SAS AF: 0.0630

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.0895

Gnomad OTH AF: 0.0991

GnomAD2 exomes AF: 0.0727 AC: 16635 AN: 228728 AF XY: 0.0749

Gnomad AFR exome AF: 0.0652

Gnomad AMR exome AF: 0.0448

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.0349

Gnomad FIN exome AF: 0.0362

Gnomad NFE exome AF: 0.0929

Gnomad OTH exome AF: 0.0907

GnomAD4 exome AF: 0.0840 AC: 119894 AN: 1427364 Hom.: 5363 Cov.: 25 AF XY: 0.0841 AC XY: 59779 AN XY: 710566

African (AFR) AF: 0.0642 AC: 2109 AN: 32864

American (AMR) AF: 0.0476 AC: 2063 AN: 43384

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3170 AN: 25768

East Asian (EAS) AF: 0.0416 AC: 1638 AN: 39398

South Asian (SAS) AF: 0.0642 AC: 5443 AN: 84842

European-Finnish (FIN) AF: 0.0388 AC: 2011 AN: 51794

Middle Eastern (MID) AF: 0.119 AC: 674 AN: 5670

European-Non Finnish (NFE) AF: 0.0901 AC: 97663 AN: 1084402

Other (OTH) AF: 0.0865 AC: 5123 AN: 59242

GnomAD4 genome AF: 0.0742 AC: 11292 AN: 152160 Hom.: 457 Cov.: 32 AF XY: 0.0717 AC XY: 5333 AN XY: 74394

African (AFR) AF: 0.0639 AC: 2655 AN: 41522

American (AMR) AF: 0.0656 AC: 1003 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.0379 AC: 196 AN: 5166

South Asian (SAS) AF: 0.0627 AC: 302 AN: 4820

European-Finnish (FIN) AF: 0.0337 AC: 357 AN: 10584

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.0895 AC: 6085 AN: 68004

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0874 Hom.: 807

Bravo AF: 0.0754

Asia WGS AF: 0.0550 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.48
PhyloP100		-0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs17265551; hg19: chr16-16150208; COSMIC: COSV60682151;