chr16-16083418-G-A

Variant names:

Variant summary

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

The NM_004996.4(ABCC1):c.2168G>A(p.Arg723Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,613,812 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R723G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.013 ( 36 hom., cov: 33)

Exomes 𝑓: 0.014 ( 368 hom. )

Consequence

ABCC1
NM_004996.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.176

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 (MetaRNN=0.0024918914).

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.2168G>A	p.Arg723Gln	missense_variant	Exon 17 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.2168G>A	p.Arg723Gln	missense_variant	Exon 17 of 31	1	NM_004996.4	ENSP00000382342.3

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2039

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0388

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.00973

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0235

AC:

5860

AN:

249542

AF XY:

0.0209

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.0789

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.0480

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0172

GnomAD4 exome

AF:

0.0144

AC:

20975

AN:

1461562

Hom.:

368

Cov.:

AF XY:

0.0140

AC XY:

10164

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.00206

AC:

AN:

33470

American (AMR)

AF:

0.0743

AC:

3323

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00945

AC:

247

AN:

26136

East Asian (EAS)

AF:

0.0614

AC:

2439

AN:

39700

South Asian (SAS)

AF:

0.00848

AC:

731

AN:

86230

European-Finnish (FIN)

AF:

0.0198

AC:

1059

AN:

53420

Middle Eastern (MID)

AF:

0.00471

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.0110

AC:

12284

AN:

1111998

Other (OTH)

AF:

0.0132

AC:

797

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1179

2358

3536

4715

5894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.0134

AC:

2043

AN:

152250

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1069

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00279

AC:

116

AN:

41546

American (AMR)

AF:

0.0388

AC:

593

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

AN:

3472

East Asian (EAS)

AF:

0.0504

AC:

261

AN:

5182

South Asian (SAS)

AF:

0.00954

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0229

AC:

243

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

721

AN:

68016

Other (OTH)

AF:

0.0128

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

104

208

311

415

519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0134

Hom.:

137

Bravo

AF:

0.0151

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0132

AC:

ESP6500AA

AF:

0.00346

AC:

ESP6500EA

AF:

0.0120

AC:

101

ExAC

AF:

0.0210

AC:

2547

Asia WGS

AF:

0.0380

AC:

131

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.00895

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Familial cancer of breast

Uncertain:1

Feb 01, 2014

Research Lab, National Institute of Public Health

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.40

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.8

L;.

PhyloP100

0.18

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.36

N;.

REVEL

Uncertain

0.29

Sift

Benign

0.82

T;.

Sift4G

Benign

0.56

T;T

Vest4

0.092

ClinPred

0.0044

GERP RS

-2.9

Varity_R

0.070

gMVP

0.39

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over