chr3-149186647-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000096.4(CP):c.1950A>C(p.Gly650Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,614,152 control chromosomes in the GnomAD database, including 2,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 191 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2641 hom. )

Consequence

CP
NM_000096.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.733

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

aceruloplasminemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
disorder of iron metabolism and transport
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 3-149186647-T-G is Benign according to our data. Variant chr3-149186647-T-G is described in ClinVar as [Benign]. Clinvar id is 128838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.733 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4 link	c.1950A>C	p.Gly650Gly	synonymous_variant	Exon 11 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.1950A>C	p.Gly650Gly	synonymous_variant	Exon 11 of 19	1	NM_000096.4	ENSP00000264613.6		P00450

Frequencies

GnomAD3 genomes

AF:

0.0417

AC:

6344

AN:

152186

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.0270

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0657

Gnomad OTH

AF:

0.0546

GnomAD2 exomes

AF:

0.0441

AC:

11080

AN:

251428

AF XY:

0.0453

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.0275

Gnomad ASJ exome

AF:

0.0680

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.0295

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0575

GnomAD4 exome

AF:

0.0571

AC:

83456

AN:

1461848

Hom.:

2641

Cov.:

AF XY:

0.0564

AC XY:

41030

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0111

AC:

373

AN:

33480

American (AMR)

AF:

0.0297

AC:

1330

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

1837

AN:

26136

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0335

AC:

2893

AN:

86256

European-Finnish (FIN)

AF:

0.0322

AC:

1719

AN:

53420

Middle Eastern (MID)

AF:

0.0662

AC:

382

AN:

5768

European-Non Finnish (NFE)

AF:

0.0643

AC:

71483

AN:

1111968

Other (OTH)

AF:

0.0568

AC:

3429

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4693

9386

14078

18771

23464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0417

AC:

6346

AN:

152304

Hom.:

191

Cov.:

AF XY:

0.0401

AC XY:

2983

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41568

American (AMR)

AF:

0.0396

AC:

606

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

215

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5192

South Asian (SAS)

AF:

0.0255

AC:

123

AN:

4820

European-Finnish (FIN)

AF:

0.0270

AC:

287

AN:

10624

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0657

AC:

4467

AN:

68022

Other (OTH)

AF:

0.0541

AC:

114

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

310

620

929

1239

1549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0560

Hom.:

517

Bravo

AF:

0.0413

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.0638

EpiControl

AF:

0.0671

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

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

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 04, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Deficiency of ferroxidase

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.4

(source)

DANN

Benign

0.70

PhyloP100

-0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=94/6

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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chr3-149186647-T-G

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