Genetic Variant CP:c.2426-126G>A (chr3-149182259-C-T) – ACMG Classification: Benign (-20 pts)

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.2426-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,049,508 control chromosomes in the GnomAD database, including 5,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 3708 hom., cov: 31)

Exomes 𝑓: 0.023 ( 2164 hom. )

Consequence

CP
NM_000096.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.767

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-149182259-C-T is Benign according to our data. Variant chr3-149182259-C-T is described in ClinVar as [Benign]. Clinvar id is 1268348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4 link	c.2426-126G>A		intron_variant	Intron 13 of 18	ENST00000264613.11	NP_000087.2	P00450A5PL27

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CP	ENST00000264613.11 link	c.2426-126G>A	intron_variant	Intron 13 of 18	1	NM_000096.4	ENSP00000264613.6	P00450
CP	ENST00000494544.1 link	c.1775-126G>A	intron_variant	Intron 10 of 15	1		ENSP00000420545.1	H7C5R1
CP	ENST00000490639.5 link	n.2458-126G>A	intron_variant	Intron 13 of 16	1
CP	ENST00000481169.5 link	n.2213-126G>A	intron_variant	Intron 12 of 17	2		ENSP00000418773.1	E9PFZ2

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19402

AN:

152020

Hom.:

3695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.420

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0484

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.0241

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.0850

GnomAD4 exome

AF:

0.0226

AC:

20279

AN:

897372

Hom.:

2164

AF XY:

0.0205

AC XY:

9536

AN XY:

464422

show subpopulations

Gnomad4 AFR exome

AF:

0.426

AC:

8991

AN:

21086

Gnomad4 AMR exome

AF:

0.0300

AC:

1130

AN:

37632

Gnomad4 ASJ exome

AF:

0.00359

AC:

AN:

22032

Gnomad4 EAS exome

AF:

0.0000578

AC:

AN:

34616

Gnomad4 SAS exome

AF:

0.00680

AC:

484

AN:

71168

Gnomad4 FIN exome

AF:

0.0205

AC:

790

AN:

38528

Gnomad4 NFE exome

AF:

0.0112

AC:

7012

AN:

626392

Gnomad4 Remaining exome

AF:

0.0391

AC:

1633

AN:

41770

Heterozygous variant carriers

792

1584

2375

3167

3959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.128

AC:

19464

AN:

152136

Hom.:

3708

Cov.:

AF XY:

0.124

AC XY:

9201

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.421

AC:

0.420699

AN:

0.420699

Gnomad4 AMR

AF:

0.0482

AC:

0.0482416

AN:

0.0482416

Gnomad4 ASJ

AF:

0.00346

AC:

0.00345622

AN:

0.00345622

Gnomad4 EAS

AF:

0.000193

AC:

0.000193125

AN:

0.000193125

Gnomad4 SAS

AF:

0.00684

AC:

0.00683513

AN:

0.00683513

Gnomad4 FIN

AF:

0.0241

AC:

0.0241373

AN:

0.0241373

Gnomad4 NFE

AF:

0.0119

AC:

0.0119373

AN:

0.0119373

Gnomad4 OTH

AF:

0.0841

AC:

0.084121

AN:

0.084121

Heterozygous variant carriers

615

1230

1845

2460

3075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0505

Hom.:

1492

Bravo

AF:

0.144

Asia WGS

AF:

0.0300

AC:

106

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 10, 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

-0.86

CADD

Benign

2.2

DANN

Benign

0.72

Mutation Taster

=100/0

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