chr16-16048222-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004996.4(ABCC1):c.1299G>T(p.Arg433Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,614,196 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 131 hom. )

Consequence

ABCC1
NM_004996.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.0320

Publications

44 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019949764).

BP6

Variant 16-16048222-G-T is Benign according to our data. Variant chr16-16048222-G-T is described in ClinVar as Benign. ClinVar VariationId is 489391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1149 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC1	NM_004996.4 link	c.1299G>T	p.Arg433Ser	missense_variant	Exon 10 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.1299G>T	p.Arg433Ser	missense_variant	Exon 10 of 31	1	NM_004996.4	ENSP00000382342.3		P33527-1

Frequencies

GnomAD3 genomes

AF:

0.00755

AC:

1149

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00890

AC:

2221

AN:

249556

AF XY:

0.00862

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00417

Gnomad ASJ exome

AF:

0.0131

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0107

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.00858

GnomAD4 exome

AF:

0.0117

AC:

17119

AN:

1461886

Hom.:

131

Cov.:

AF XY:

0.0114

AC XY:

8269

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00206

AC:

AN:

33480

American (AMR)

AF:

0.00436

AC:

195

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0129

AC:

338

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00260

AC:

224

AN:

86258

European-Finnish (FIN)

AF:

0.0111

AC:

594

AN:

53420

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0136

AC:

15079

AN:

1112006

Other (OTH)

AF:

0.00988

AC:

597

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

995

1990

2986

3981

4976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.00754

AC:

1149

AN:

152310

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

507

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41568

American (AMR)

AF:

0.00386

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00290

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00942

AC:

100

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0124

AC:

843

AN:

68030

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0112

Hom.:

Bravo

AF:

0.00691

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00168

AC:

ESP6500EA

AF:

0.0122

AC:

103

ExAC

AF:

0.00937

AC:

1134

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ABCC1: BS1, BS2 -

Aug 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;T

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.80

LIST_S2

Pathogenic

0.98

D;D

MetaRNN

Benign

0.020

T;T

MetaSVM

Uncertain

0.43

MutationAssessor

Uncertain

2.7

M;.

PhyloP100

-0.032

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.1

D;.

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

D;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.93

MutPred

0.29

Loss of catalytic residue at R433 (P = 0.1193);.;

MVP

0.93

MPC

1.1

ClinPred

0.044

GERP RS

-0.26

Varity_R

0.86

gMVP

0.97

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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