dbSNP rs3743527: ABCC1:c.*543C>T (chr16-16141824-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004996.4(ABCC1):c.*543C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 154,262 control chromosomes in the GnomAD database, including 4,053 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 0.21 ( 3996 hom., cov: 32)

Exomes 𝑓: 0.21 ( 57 hom. )

Consequence

ABCC1
NM_004996.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.376

Publications

48 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.*543C>T		3_prime_UTR_variant	Exon 31 of 31	ENST00000399410.8	NP_004987.2	P33527-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC1	ENST00000399410.8 link	c.*543C>T		3_prime_UTR_variant	Exon 31 of 31	1	NM_004996.4	ENSP00000382342.3		P33527-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32665

AN:

151918

Hom.:

3999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.199

GnomAD4 exome

AF:

0.212

AC:

471

AN:

2224

Hom.:

Cov.:

AF XY:

0.202

AC XY:

234

AN XY:

1160

show subpopulations

African (AFR)

AF:

0.182

AC:

AN:

American (AMR)

AF:

0.200

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

AN:

East Asian (EAS)

AF:

0.352

AC:

AN:

142

South Asian (SAS)

AF:

0.400

AC:

AN:

European-Finnish (FIN)

AF:

0.342

AC:

AN:

146

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.186

AC:

297

AN:

1600

Other (OTH)

AF:

0.221

AC:

AN:

104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.215

AC:

32678

AN:

152038

Hom.:

3996

Cov.:

AF XY:

0.224

AC XY:

16651

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.147

AC:

6093

AN:

41460

American (AMR)

AF:

0.214

AC:

3275

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

724

AN:

3466

East Asian (EAS)

AF:

0.441

AC:

2264

AN:

5132

South Asian (SAS)

AF:

0.452

AC:

2180

AN:

4826

European-Finnish (FIN)

AF:

0.297

AC:

3146

AN:

10584

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14396

AN:

67978

Other (OTH)

AF:

0.199

AC:

420

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1280

2560

3839

5119

6399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.213

Hom.:

13715

Bravo

AF:

0.204

Asia WGS

AF:

0.375

AC:

1303

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.55

(source)

DANN

Benign

0.31

PhyloP100

-0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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