rs212088

Variant names:

• chr16-16138576-G-A
• rs212088
• NM_004996.4:c.4487+18G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-16138576-G-A
• chr16-16138576-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.4487+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,549,228 control chromosomes in the GnomAD database, including 24,529 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 0.16 (1901 hom., cov: 31)
  • Exomes 𝑓: 0.18 (22628 hom.)
• Consequence: ABCC1 NM_004996.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4	c.4487+18G>A		intron_variant	Intron 30 of 30	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8	c.4487+18G>A		intron_variant	Intron 30 of 30	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23703 AN: 152038 Hom.: 1901 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.160 AC: 34010 AN: 212392 AF XY: 0.162

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.122

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.176 AC: 246555 AN: 1397072 Hom.: 22628 Cov.: 32 AF XY: 0.175 AC XY: 120103 AN XY: 686858

African (AFR) AF: 0.130 AC: 4162 AN: 32052

American (AMR) AF: 0.115 AC: 4617 AN: 39998

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2795 AN: 23690

East Asian (EAS) AF: 0.259 AC: 9820 AN: 37914

South Asian (SAS) AF: 0.112 AC: 8893 AN: 79482

European-Finnish (FIN) AF: 0.121 AC: 6161 AN: 50784

Middle Eastern (MID) AF: 0.180 AC: 919 AN: 5098

European-Non Finnish (NFE) AF: 0.186 AC: 199542 AN: 1070628

Other (OTH) AF: 0.168 AC: 9646 AN: 57426

GnomAD4 genome AF: 0.156 AC: 23702 AN: 152156 Hom.: 1901 Cov.: 31 AF XY: 0.154 AC XY: 11482 AN XY: 74400

African (AFR) AF: 0.133 AC: 5512 AN: 41516

American (AMR) AF: 0.153 AC: 2332 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1259 AN: 5166

South Asian (SAS) AF: 0.107 AC: 519 AN: 4828

European-Finnish (FIN) AF: 0.116 AC: 1227 AN: 10604

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11931 AN: 67968

Other (OTH) AF: 0.167 AC: 352 AN: 2110

Alfa AF: 0.155 Hom.: 660

Bravo AF: 0.159

Asia WGS AF: 0.154 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.54
DANN	Benign	0.35
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs212088; hg19: chr16-16232433; COSMIC: COSV60687621;