rs3887893

Variant names:

• chr16-16111644-T-C
• rs3887893
• NM_004996.4:c.3079+62T>C

Your query was ambiguous. Multiple possible variants found:

• chr16-16111644-T-C
• chr16-16111644-T-G

Variant summary

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

The NM_004996.4(ABCC1):​c.3079+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,468,488 control chromosomes in the GnomAD database, including 124,566 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 0.40 (12065 hom., cov: 32)
  • Exomes 𝑓: 0.41 (112501 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• Publications: 16 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.3079+62T>C		intron_variant	Intron 22 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.3079+62T>C		intron_variant	Intron 22 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60359 AN: 151848 Hom.: 12045 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.410 AC: 540182 AN: 1316522 Hom.: 112501 AF XY: 0.415 AC XY: 271297 AN XY: 653908

African (AFR) AF: 0.386 AC: 11687 AN: 30288

American (AMR) AF: 0.335 AC: 11803 AN: 35214

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 10822 AN: 23998

East Asian (EAS) AF: 0.534 AC: 19460 AN: 36416

South Asian (SAS) AF: 0.555 AC: 43391 AN: 78202

European-Finnish (FIN) AF: 0.393 AC: 18588 AN: 47300

Middle Eastern (MID) AF: 0.454 AC: 1749 AN: 3854

European-Non Finnish (NFE) AF: 0.397 AC: 399136 AN: 1005914

Other (OTH) AF: 0.426 AC: 23546 AN: 55336

GnomAD4 genome AF: 0.398 AC: 60421 AN: 151966 Hom.: 12065 Cov.: 32 AF XY: 0.401 AC XY: 29753 AN XY: 74288

African (AFR) AF: 0.377 AC: 15601 AN: 41430

American (AMR) AF: 0.334 AC: 5114 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1473 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2817 AN: 5148

South Asian (SAS) AF: 0.554 AC: 2672 AN: 4820

European-Finnish (FIN) AF: 0.392 AC: 4137 AN: 10546

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.404 AC: 27455 AN: 67950

Other (OTH) AF: 0.392 AC: 827 AN: 2108

Alfa AF: 0.407 Hom.: 21238

Bravo AF: 0.391

Asia WGS AF: 0.492 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.013
DANN	Benign	0.44
PhyloP100		-3.0
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: rs3887893; hg19: chr16-16205501;