chr16-16090365-CAT-C

Variant names:

• chr16-16090365-CAT-C
• rs45607032
• NM_004996.4:c.2461-39_2461-38delAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004996.4(ABCC1):​c.2461-39_2461-38delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 1,536,314 control chromosomes in the GnomAD database, including 501 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.028 (91 hom., cov: 32)
  • Exomes 𝑓: 0.016 (410 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.2461-39_2461-38delAT		intron_variant	Intron 18 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.2461-39_2461-38delAT		intron_variant	Intron 18 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4269 AN: 152214 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.0294 AC: 5607 AN: 190466 AF XY: 0.0259

Gnomad AFR exome AF: 0.0494

Gnomad AMR exome AF: 0.0834

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.0505

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0131

Gnomad OTH exome AF: 0.0217

GnomAD4 exome AF: 0.0161 AC: 22294 AN: 1383982 Hom.: 410 AF XY: 0.0156 AC XY: 10560 AN XY: 678856

African (AFR) AF: 0.0512 AC: 1624 AN: 31734

American (AMR) AF: 0.0782 AC: 2917 AN: 37294

Ashkenazi Jewish (ASJ) AF: 0.0197 AC: 429 AN: 21820

East Asian (EAS) AF: 0.0622 AC: 2377 AN: 38204

South Asian (SAS) AF: 0.00879 AC: 653 AN: 74308

European-Finnish (FIN) AF: 0.0197 AC: 969 AN: 49124

Middle Eastern (MID) AF: 0.0157 AC: 83 AN: 5302

European-Non Finnish (NFE) AF: 0.0114 AC: 12211 AN: 1069218

Other (OTH) AF: 0.0181 AC: 1031 AN: 56978

GnomAD4 genome AF: 0.0281 AC: 4276 AN: 152332 Hom.: 91 Cov.: 32 AF XY: 0.0281 AC XY: 2094 AN XY: 74484

African (AFR) AF: 0.0502 AC: 2088 AN: 41584

American (AMR) AF: 0.0485 AC: 741 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.0510 AC: 264 AN: 5176

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4832

European-Finnish (FIN) AF: 0.0229 AC: 243 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 764 AN: 68030

Other (OTH) AF: 0.0269 AC: 57 AN: 2116

Alfa AF: 0.0220 Hom.: 14

Bravo AF: 0.0324

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.0
Mutation Taster		=88/12	polymorphism

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: rs45607032; hg19: chr16-16184222; COSMIC: COSV107406340; COSMIC: COSV107406340;