NM_004996.4:c.1474-48C>T

Variant names:

• chr16-16056044-C-T
• rs3765129
• NM_004996.4:c.1474-48C>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.1474-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,545,676 control chromosomes in the GnomAD database, including 16,013 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 0.11 (1299 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14714 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 16 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 (AMR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1474-48C>T		intron_variant	Intron 11 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.1474-48C>T		intron_variant	Intron 11 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17440 AN: 152040 Hom.: 1299 Cov.: 32

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.0948

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.134 AC: 32689 AN: 244506 AF XY: 0.129

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.0938

Gnomad EAS exome AF: 0.0962

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.140 AC: 195211 AN: 1393518 Hom.: 14714 Cov.: 24 AF XY: 0.138 AC XY: 95441 AN XY: 693986

African (AFR) AF: 0.0219 AC: 703 AN: 32030

American (AMR) AF: 0.177 AC: 7761 AN: 43876

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 2403 AN: 25310

East Asian (EAS) AF: 0.0988 AC: 3861 AN: 39096

South Asian (SAS) AF: 0.0537 AC: 4535 AN: 84484

European-Finnish (FIN) AF: 0.209 AC: 11054 AN: 52918

Middle Eastern (MID) AF: 0.0812 AC: 454 AN: 5594

European-Non Finnish (NFE) AF: 0.149 AC: 157207 AN: 1052312

Other (OTH) AF: 0.125 AC: 7233 AN: 57898

GnomAD4 genome AF: 0.115 AC: 17439 AN: 152158 Hom.: 1299 Cov.: 32 AF XY: 0.116 AC XY: 8628 AN XY: 74368

African (AFR) AF: 0.0276 AC: 1145 AN: 41536

American (AMR) AF: 0.151 AC: 2309 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0933 AC: 323 AN: 3462

East Asian (EAS) AF: 0.0951 AC: 492 AN: 5176

South Asian (SAS) AF: 0.0436 AC: 210 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2148 AN: 10554

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10271 AN: 68012

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.135 Hom.: 1952

Bravo AF: 0.109

Asia WGS AF: 0.0770 AC: 269 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	4.7
DANN	Benign	0.63
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3765129; hg19: chr16-16149901; COSMIC: COSV60686572;