chr16-16079364-C-T

Variant names:

• chr16-16079364-C-T
• rs8187863
• NM_004996.4:c.2001C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004996.4(ABCC1):​c.2001C>T​(p.Ser667Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,613,984 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (15 hom., cov: 32)
  • Exomes 𝑓: 0.013 (162 hom.)
• Consequence: ABCC1 NM_004996.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.930
• Publications: 12 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 16-16079364-C-T is Benign according to our data. Variant chr16-16079364-C-T is described in ClinVar as Benign. ClinVar VariationId is 4083528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 2071 AD,Unknown gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	NM_004996.4	MANE Select	c.2001C>T	p.Ser667Ser	synonymous	Exon 16 of 31	NP_004987.2
	ABCC1	NM_019901.2		c.1875C>T	p.Ser625Ser	synonymous	Exon 15 of 30	NP_063956.2
	ABCC1	NM_019902.2		c.1854C>T	p.Ser618Ser	synonymous	Exon 15 of 30	NP_063957.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCC1	ENST00000399410.8	TSL:1 MANE Select	c.2001C>T	p.Ser667Ser	synonymous	Exon 16 of 31	ENSP00000382342.3
	ABCC1	ENST00000572882.3	TSL:1	c.2001C>T	p.Ser667Ser	synonymous	Exon 16 of 30	ENSP00000461615.2
	ABCC1	ENST00000399408.7	TSL:5	c.2001C>T	p.Ser667Ser	synonymous	Exon 16 of 32	ENSP00000382340.4

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2067 AN: 152190 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0275

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.00909

GnomAD2 exomes AF: 0.0132 AC: 3279 AN: 249128 AF XY: 0.0126

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.00829

Gnomad ASJ exome AF: 0.0172

Gnomad EAS exome AF: 0.00295

Gnomad FIN exome AF: 0.0253

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0163

GnomAD4 exome AF: 0.0130 AC: 19026 AN: 1461676 Hom.: 162 Cov.: 30 AF XY: 0.0128 AC XY: 9291 AN XY: 727156

African (AFR) AF: 0.0104 AC: 349 AN: 33478

American (AMR) AF: 0.00892 AC: 399 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 511 AN: 26128

East Asian (EAS) AF: 0.00310 AC: 123 AN: 39700

South Asian (SAS) AF: 0.00132 AC: 114 AN: 86242

European-Finnish (FIN) AF: 0.0259 AC: 1384 AN: 53380

Middle Eastern (MID) AF: 0.0175 AC: 101 AN: 5764

European-Non Finnish (NFE) AF: 0.0137 AC: 15224 AN: 1111890

Other (OTH) AF: 0.0136 AC: 821 AN: 60380

GnomAD4 genome AF: 0.0136 AC: 2071 AN: 152308 Hom.: 15 Cov.: 32 AF XY: 0.0145 AC XY: 1082 AN XY: 74482

African (AFR) AF: 0.0109 AC: 452 AN: 41572

American (AMR) AF: 0.0101 AC: 154 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.00271 AC: 14 AN: 5172

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.0275 AC: 292 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1059 AN: 68030

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.0152 Hom.: 83

Bravo AF: 0.0121

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0148

EpiControl AF: 0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ABCC1: BS1, BS2

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	16
DANN	Benign	0.63
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: 11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8187863; hg19: chr16-16173221;