16-16138344-GTT-GT

Variant names:

• chr16-16138344-GT-G
• rs4148379
• NM_004996.4:c.4293-13delT

Variant summary

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

The NM_004996.4(ABCC1):​c.4293-13delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,564,714 control chromosomes in the GnomAD database, including 49,856 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4229 hom., cov: 24)
  • Exomes 𝑓: 0.24 (45627 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 2 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):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 77

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004996.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.4293-13delT		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.4167-13delT		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.4146-13delT		intron	N/A	NP_063957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.4293-19delT		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.4116-19delT		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000914156.1		c.4449-19delT		intron	N/A	ENSP00000584215.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33731 AN: 151820 Hom.: 4235 Cov.: 24

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.209

GnomAD2 exomes AF: 0.282 AC: 65232 AN: 230948 AF XY: 0.287

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.447

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.244 AC: 345253 AN: 1412776 Hom.: 45627 Cov.: 24 AF XY: 0.251 AC XY: 174209 AN XY: 695362

African (AFR) AF: 0.148 AC: 4832 AN: 32606

American (AMR) AF: 0.304 AC: 12798 AN: 42056

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5509 AN: 24300

East Asian (EAS) AF: 0.389 AC: 14959 AN: 38488

South Asian (SAS) AF: 0.450 AC: 36934 AN: 82120

European-Finnish (FIN) AF: 0.298 AC: 15581 AN: 52284

Middle Eastern (MID) AF: 0.303 AC: 1669 AN: 5510

European-Non Finnish (NFE) AF: 0.221 AC: 238424 AN: 1077372

Other (OTH) AF: 0.251 AC: 14547 AN: 58040

GnomAD4 genome AF: 0.222 AC: 33740 AN: 151938 Hom.: 4229 Cov.: 24 AF XY: 0.230 AC XY: 17098 AN XY: 74226

African (AFR) AF: 0.149 AC: 6187 AN: 41466

American (AMR) AF: 0.224 AC: 3413 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3468

East Asian (EAS) AF: 0.436 AC: 2247 AN: 5148

South Asian (SAS) AF: 0.451 AC: 2171 AN: 4816

European-Finnish (FIN) AF: 0.297 AC: 3124 AN: 10518

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15194 AN: 67956

Other (OTH) AF: 0.209 AC: 440 AN: 2104

Alfa AF: 0.227 Hom.: 729

Bravo AF: 0.212

Asia WGS AF: 0.378 AC: 1315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.063
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: rs4148379; hg19: chr16-16232201; COSMIC: COSV107406341;