rs701753

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000096.4(CP):c.1632A>T(p.Glu544Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 1,609,336 control chromosomes in the GnomAD database, including 691,101 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58829 hom., cov: 31)

Exomes 𝑓: 0.93 ( 632272 hom. )

Consequence

CP
NM_000096.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0930

Variant links:

Genes affected

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

CP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0621669E-6).

BP6

Variant 3-149198448-T-A is Benign according to our data. Variant chr3-149198448-T-A is described in ClinVar as [Benign]. Clinvar id is 198992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-149198448-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4 link	c.1632A>T	p.Glu544Asp	missense_variant	Exon 9 of 19	ENST00000264613.11	NP_000087.2	P00450A5PL27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11 link	c.1632A>T	p.Glu544Asp	missense_variant	Exon 9 of 19	1	NM_000096.4	ENSP00000264613.6		P00450

Frequencies

GnomAD3 genomes

AF:

0.873

AC:

132690

AN:

152002

Hom.:

58797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.941

Gnomad AMR

AF:

0.940

Gnomad ASJ

AF:

0.935

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.877

Gnomad FIN

AF:

0.942

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.939

Gnomad OTH

AF:

0.898

GnomAD2 exomes

AF:

0.923

AC:

231447

AN:

250842

AF XY:

0.922

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.956

Gnomad ASJ exome

AF:

0.938

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.941

Gnomad NFE exome

AF:

0.941

Gnomad OTH exome

AF:

0.928

GnomAD4 exome

AF:

0.930

AC:

1355729

AN:

1457216

Hom.:

632272

Cov.:

AF XY:

0.929

AC XY:

673906

AN XY:

725250

show subpopulations

Gnomad4 AFR exome

AF:

0.685

AC:

22764

AN:

33240

Gnomad4 AMR exome

AF:

0.953

AC:

42596

AN:

44714

Gnomad4 ASJ exome

AF:

0.938

AC:

24483

AN:

26106

Gnomad4 EAS exome

AF:

1.00

AC:

39684

AN:

39692

Gnomad4 SAS exome

AF:

0.873

AC:

75176

AN:

86112

Gnomad4 FIN exome

AF:

0.943

AC:

50336

AN:

53406

Gnomad4 NFE exome

AF:

0.939

AC:

1039932

AN:

1107952

Gnomad4 Remaining exome

AF:

0.924

AC:

55660

AN:

60250

Heterozygous variant carriers

4089

8178

12267

16356

20445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

21444

42888

64332

85776

107220

<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:

0.873

AC:

132774

AN:

152120

Hom.:

58829

Cov.:

AF XY:

0.873

AC XY:

64906

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.698

AC:

0.698156

AN:

0.698156

Gnomad4 AMR

AF:

0.940

AC:

0.93978

AN:

0.93978

Gnomad4 ASJ

AF:

0.935

AC:

0.934582

AN:

0.934582

Gnomad4 EAS

AF:

0.999

AC:

0.999227

AN:

0.999227

Gnomad4 SAS

AF:

0.876

AC:

0.876351

AN:

0.876351

Gnomad4 FIN

AF:

0.942

AC:

0.94242

AN:

0.94242

Gnomad4 NFE

AF:

0.938

AC:

0.938494

AN:

0.938494

Gnomad4 OTH

AF:

0.900

AC:

0.899716

AN:

0.899716

Heterozygous variant carriers

780

1561

2341

3122

3902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.906

Hom.:

11546

Bravo

AF:

0.866

ESP6500AA

AF:

0.699

AC:

3080

ESP6500EA

AF:

0.936

AC:

8024

ExAC

AF:

0.916

AC:

111255

EpiCase

AF:

0.933

EpiControl

AF:

0.932

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 21, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Deficiency of ferroxidase

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

5.6

DANN

Benign

0.44

DEOGEN2

Benign

0.0070

.;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.24

.;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.41

PROVEAN

Benign

2.9

N;N

REVEL

Uncertain

0.30

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.022

MutPred

0.49

Gain of ubiquitination at K547 (P = 0.0632);.;

MPC

0.085

ClinPred

0.0051

GERP RS

-2.5

gMVP

0.67

Mutation Taster

=98/2

polymorphism (auto)

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over