16-15991379-C-T

Variant names:

• chr16-15991379-C-T
• rs152023
• NM_004996.4:c.49-16437C>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.49-16437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,852 control chromosomes in the GnomAD database, including 27,134 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 0.58 (27134 hom., cov: 30)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 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.49-16437C>T		intron	N/A	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.49-16437C>T		intron	N/A	NP_063956.2
	ABCC1	NM_019902.2		c.49-16437C>T		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.49-16437C>T		intron	N/A	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.49-16437C>T		intron	N/A	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000574224.2	TSL:1	n.124-16437C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88082 AN: 151734 Hom.: 27125 Cov.: 30

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.580 AC: 88105 AN: 151852 Hom.: 27134 Cov.: 30 AF XY: 0.580 AC XY: 43021 AN XY: 74200

African (AFR) AF: 0.350 AC: 14503 AN: 41378

American (AMR) AF: 0.609 AC: 9282 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2295 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3381 AN: 5154

South Asian (SAS) AF: 0.722 AC: 3473 AN: 4808

European-Finnish (FIN) AF: 0.642 AC: 6775 AN: 10550

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46467 AN: 67950

Other (OTH) AF: 0.596 AC: 1253 AN: 2104

Alfa AF: 0.646 Hom.: 59555

Bravo AF: 0.563

Asia WGS AF: 0.646 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.74
DANN	Benign	0.79
PhyloP100		-1.1
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: rs152023; hg19: chr16-16085236;