dbSNP rs8187863: ABCC1:p.Ser667Ser (chr16-16079364-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.930

Publications

12 publications found

Variant links:

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

ABCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.2001C>T	p.Ser667Ser	synonymous_variant	Exon 16 of 31	ENST00000399410.8	NP_004987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8 link	c.2001C>T	p.Ser667Ser	synonymous_variant	Exon 16 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2067

AN:

152190

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0128

AC XY:

9291

AN XY:

727156

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1041

2082

3124

4165

5206

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

518

1036

1554

2072

2590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0136

AC:

2071

AN:

152308

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1082

AN XY:

74482

show subpopulations

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:

AN:

3472

East Asian (EAS)

AF:

0.00271

AC:

AN:

5172

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0275

AC:

292

AN:

10620

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0156

AC:

1059

AN:

68030

Other (OTH)

AF:

0.00900

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

103

205

308

410

513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0148

EpiControl

AF:

0.0152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

-0.93

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over