rs8187843

Variant names:

• chr16-16008018-G-A
• rs8187843
• NM_004996.4:c.225+26G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-16008018-G-A
• chr16-16008018-G-C
• chr16-16008018-G-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.225+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 577,782 control chromosomes in the GnomAD database, including 4,122 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 0.051 (237 hom., cov: 29)
  • Exomes 𝑓: 0.19 (3885 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• 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):

• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.225+26G>A		intron_variant	Intron 2 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.225+26G>A		intron_variant	Intron 2 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7213 AN: 141906 Hom.: 237 Cov.: 29

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0486

Gnomad EAS AF: 0.000944

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0587

GnomAD2 exomes AF: 0.0534 AC: 10139 AN: 189756 AF XY: 0.0533

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.0435

Gnomad ASJ exome AF: 0.0499

Gnomad EAS exome AF: 0.000170

Gnomad FIN exome AF: 0.0624

Gnomad NFE exome AF: 0.0734

Gnomad OTH exome AF: 0.0688

GnomAD4 exome AF: 0.189 AC: 82324 AN: 435740 Hom.: 3885 Cov.: 8 AF XY: 0.171 AC XY: 40213 AN XY: 235726

African (AFR) AF: 0.0572 AC: 416 AN: 7278

American (AMR) AF: 0.0583 AC: 1306 AN: 22410

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1031 AN: 9786

East Asian (EAS) AF: 0.000101 AC: 1 AN: 9854

South Asian (SAS) AF: 0.0249 AC: 1326 AN: 53168

European-Finnish (FIN) AF: 0.0913 AC: 2996 AN: 32814

Middle Eastern (MID) AF: 0.166 AC: 485 AN: 2930

European-Non Finnish (NFE) AF: 0.255 AC: 71464 AN: 279718

Other (OTH) AF: 0.186 AC: 3299 AN: 17782

GnomAD4 genome AF: 0.0508 AC: 7221 AN: 142042 Hom.: 237 Cov.: 29 AF XY: 0.0509 AC XY: 3499 AN XY: 68798

African (AFR) AF: 0.0144 AC: 568 AN: 39358

American (AMR) AF: 0.0526 AC: 748 AN: 14212

Ashkenazi Jewish (ASJ) AF: 0.0486 AC: 162 AN: 3334

East Asian (EAS) AF: 0.000944 AC: 4 AN: 4236

South Asian (SAS) AF: 0.0188 AC: 74 AN: 3934

European-Finnish (FIN) AF: 0.0686 AC: 612 AN: 8916

Middle Eastern (MID) AF: 0.142 AC: 40 AN: 282

European-Non Finnish (NFE) AF: 0.0736 AC: 4778 AN: 64904

Other (OTH) AF: 0.0581 AC: 116 AN: 1998

Alfa AF: 0.0599 Hom.: 974

Bravo AF: 0.0452

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		0.28
Mutation Taster		=99/1	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: rs8187843; hg19: chr16-16101875;