rs2283512

Variant names:

• chr16-16126345-A-C
• rs2283512
• NM_004996.4:c.3819+434A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-16126345-A-C
• chr16-16126345-A-G
• chr16-16126345-A-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.3819+434A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,024 control chromosomes in the GnomAD database, including 28,254 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 0.59 (28254 hom., cov: 32)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.3819+434A>C		intron_variant	Intron 26 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.3819+434A>C		intron_variant	Intron 26 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90065 AN: 151906 Hom.: 28257 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.593 AC: 90081 AN: 152024 Hom.: 28254 Cov.: 32 AF XY: 0.594 AC XY: 44141 AN XY: 74304

African (AFR) AF: 0.365 AC: 15141 AN: 41454

American (AMR) AF: 0.626 AC: 9558 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2508 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2746 AN: 5164

South Asian (SAS) AF: 0.659 AC: 3172 AN: 4816

European-Finnish (FIN) AF: 0.680 AC: 7186 AN: 10564

Middle Eastern (MID) AF: 0.729 AC: 213 AN: 292

European-Non Finnish (NFE) AF: 0.699 AC: 47483 AN: 67966

Other (OTH) AF: 0.637 AC: 1346 AN: 2112

Alfa AF: 0.671 Hom.: 36336

Bravo AF: 0.575

Asia WGS AF: 0.613 AC: 2132 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	1.4
DANN	Benign	0.63
PhyloP100		-0.19
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: rs2283512; hg19: chr16-16220202;