rs2230671

Variant names:

• chr16-16134385-G-A
• rs2230671
• NM_004996.4:c.4002G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-16134385-G-A
• chr16-16134385-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004996.4(ABCC1):​c.4002G>A​(p.Ser1334Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,613,802 control chromosomes in the GnomAD database, including 57,722 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 0.22 (4412 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53310 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 37 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):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 77

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-1.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004996.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.4002G>A	p.Ser1334Ser	synonymous	Exon 28 of 31	NP_004987.2	P33527-1
	ABCC1	NM_019901.2		c.3876G>A	p.Ser1292Ser	synonymous	Exon 27 of 30	NP_063956.2
	ABCC1	NM_019902.2		c.3855G>A	p.Ser1285Ser	synonymous	Exon 27 of 30	NP_063957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.4002G>A	p.Ser1334Ser	synonymous	Exon 28 of 31	ENSP00000382342.3	P33527-1
	ABCC1	ENST00000572882.3	TSL:1	c.3825G>A	p.Ser1275Ser	synonymous	Exon 27 of 30	ENSP00000461615.2	P33527-2
	ABCC1	ENST00000914156.1		c.4158G>A	p.Ser1386Ser	synonymous	Exon 29 of 32	ENSP00000584215.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34014 AN: 151846 Hom.: 4410 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.249 AC: 62090 AN: 249422 AF XY: 0.247

Gnomad AFR exome AF: 0.0934

Gnomad AMR exome AF: 0.310

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.115

Gnomad FIN exome AF: 0.332

Gnomad NFE exome AF: 0.279

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.265 AC: 387966 AN: 1461838 Hom.: 53310 Cov.: 38 AF XY: 0.263 AC XY: 190942 AN XY: 727220

African (AFR) AF: 0.0915 AC: 3064 AN: 33480

American (AMR) AF: 0.310 AC: 13853 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5694 AN: 26136

East Asian (EAS) AF: 0.139 AC: 5529 AN: 39700

South Asian (SAS) AF: 0.176 AC: 15167 AN: 86258

European-Finnish (FIN) AF: 0.325 AC: 17339 AN: 53390

Middle Eastern (MID) AF: 0.176 AC: 1013 AN: 5768

European-Non Finnish (NFE) AF: 0.280 AC: 311617 AN: 1111988

Other (OTH) AF: 0.243 AC: 14690 AN: 60394

GnomAD4 genome AF: 0.224 AC: 34022 AN: 151964 Hom.: 4412 Cov.: 32 AF XY: 0.225 AC XY: 16714 AN XY: 74258

African (AFR) AF: 0.0977 AC: 4052 AN: 41466

American (AMR) AF: 0.288 AC: 4396 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 776 AN: 3466

East Asian (EAS) AF: 0.118 AC: 602 AN: 5120

South Asian (SAS) AF: 0.169 AC: 811 AN: 4812

European-Finnish (FIN) AF: 0.337 AC: 3555 AN: 10554

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19027 AN: 67954

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.262 Hom.: 10987

Bravo AF: 0.213

Asia WGS AF: 0.149 AC: 518 AN: 3478

EpiCase AF: 0.267

EpiControl AF: 0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.43
DANN	Benign	0.66
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs2230671; hg19: chr16-16228242; COSMIC: COSV60679240;