16-16068071-G-A

Variant names:

• chr16-16068071-G-A
• rs4148348
• NM_004996.4:c.1678-85G>A

Variant summary

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

The NM_004996.4(ABCC1):​c.1678-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,547,218 control chromosomes in the GnomAD database, including 3,497 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 0.057 (338 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3159 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.75
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.1678-85G>A		intron_variant	Intron 12 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.1678-85G>A		intron_variant	Intron 12 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8727 AN: 152050 Hom.: 337 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.0716

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.0701

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0613

Gnomad OTH AF: 0.0612

GnomAD4 exome AF: 0.0625 AC: 87178 AN: 1395050 Hom.: 3159 AF XY: 0.0628 AC XY: 43488 AN XY: 692330

African (AFR) AF: 0.0106 AC: 344 AN: 32476

American (AMR) AF: 0.0656 AC: 2822 AN: 43002

Ashkenazi Jewish (ASJ) AF: 0.0669 AC: 1630 AN: 24356

East Asian (EAS) AF: 0.0926 AC: 3618 AN: 39074

South Asian (SAS) AF: 0.0652 AC: 5391 AN: 82696

European-Finnish (FIN) AF: 0.150 AC: 6643 AN: 44174

Middle Eastern (MID) AF: 0.144 AC: 805 AN: 5604

European-Non Finnish (NFE) AF: 0.0583 AC: 62093 AN: 1065628

Other (OTH) AF: 0.0660 AC: 3832 AN: 58040

GnomAD4 genome AF: 0.0574 AC: 8728 AN: 152168 Hom.: 338 Cov.: 32 AF XY: 0.0635 AC XY: 4722 AN XY: 74376

African (AFR) AF: 0.0111 AC: 463 AN: 41544

American (AMR) AF: 0.0842 AC: 1288 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 248 AN: 3466

East Asian (EAS) AF: 0.0692 AC: 357 AN: 5156

South Asian (SAS) AF: 0.0697 AC: 336 AN: 4818

European-Finnish (FIN) AF: 0.157 AC: 1661 AN: 10580

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0613 AC: 4167 AN: 68002

Other (OTH) AF: 0.0606 AC: 128 AN: 2112

Alfa AF: 0.0516 Hom.: 170

Bravo AF: 0.0463

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.50
PhyloP100		-4.7
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: rs4148348; hg19: chr16-16161928;