16-16017034-G-A

Variant names:

• chr16-16017034-G-A
• rs3784862
• NM_004996.4:c.615+413G>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.615+413G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,978 control chromosomes in the GnomAD database, including 37,422 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 0.70 (37422 hom., cov: 31)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.52
• Publications: 22 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.615+413G>A		intron_variant	Intron 5 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.615+413G>A		intron_variant	Intron 5 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105791 AN: 151860 Hom.: 37414 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.696 AC: 105838 AN: 151978 Hom.: 37422 Cov.: 31 AF XY: 0.685 AC XY: 50893 AN XY: 74256

African (AFR) AF: 0.687 AC: 28461 AN: 41432

American (AMR) AF: 0.672 AC: 10265 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2560 AN: 3472

East Asian (EAS) AF: 0.368 AC: 1892 AN: 5144

South Asian (SAS) AF: 0.498 AC: 2399 AN: 4816

European-Finnish (FIN) AF: 0.669 AC: 7048 AN: 10542

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50937 AN: 67996

Other (OTH) AF: 0.693 AC: 1459 AN: 2106

Alfa AF: 0.728 Hom.: 121248

Bravo AF: 0.694

Asia WGS AF: 0.435 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0050
DANN	Benign	0.41
PhyloP100		-5.5
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: rs3784862; hg19: chr16-16110891;