dbSNP rs16861582: CP:c.2662-12T>C (chr3-149178643-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000096.4(CP):c.2662-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,573,888 control chromosomes in the GnomAD database, including 70,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8898 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61361 hom. )

Consequence

CP
NM_000096.4 intron

Scores

Splicing: ADA: 0.0001142

Clinical Significance

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

Conservation

PhyloP100: 0.693

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-149178643-A-G is Benign according to our data. Variant chr3-149178643-A-G is described in ClinVar as [Benign]. Clinvar id is 194589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-149178643-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4 link	c.2662-12T>C		intron_variant	Intron 15 of 18	ENST00000264613.11	NP_000087.2	P00450A5PL27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11 link	c.2662-12T>C		intron_variant	Intron 15 of 18	1	NM_000096.4	ENSP00000264613.6		P00450

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50126

AN:

151884

Hom.:

8889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.178

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.295

AC:

71017

AN:

241012

Hom.:

11028

AF XY:

0.294

AC XY:

38340

AN XY:

130572

show subpopulations

Gnomad AFR exome

AF:

0.445

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.368

Gnomad SAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.291

AC:

413383

AN:

1421886

Hom.:

61361

Cov.:

AF XY:

0.290

AC XY:

205778

AN XY:

709336

show subpopulations

Gnomad4 AFR exome

AF:

0.449

Gnomad4 AMR exome

AF:

0.213

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.363

Gnomad4 NFE exome

AF:

0.287

Gnomad4 OTH exome

AF:

0.287

GnomAD4 genome

AF:

0.330

AC:

50180

AN:

152002

Hom.:

8898

Cov.:

AF XY:

0.332

AC XY:

24671

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.178

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.296

Gnomad4 FIN

AF:

0.388

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.291

Hom.:

5032

Bravo

AF:

0.327

Asia WGS

AF:

0.335

AC:

1164

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

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

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

- -

Jan 12, 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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.2

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.020

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