Genetic Variant ENST00000489736.5:n.1686C>T (chr3-149186136-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000489736.5(CP):n.1686C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 285,278 control chromosomes in the GnomAD database, including 32,364 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 15583 hom., cov: 33)

Exomes 𝑓: 0.49 ( 16781 hom. )

Consequence

CP
ENST00000489736.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

10 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4 link	c.2077+384C>T		intron_variant	Intron 11 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.2077+384C>T		intron_variant	Intron 11 of 18	1	NM_000096.4	ENSP00000264613.6		P00450

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64529

AN:

151976

Hom.:

15579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.541

Gnomad EAS

AF:

0.543

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.453

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.455

GnomAD4 exome

AF:

0.490

AC:

65297

AN:

133184

Hom.:

16781

Cov.:

AF XY:

0.479

AC XY:

33816

AN XY:

70564

show subpopulations

African (AFR)

AF:

0.176

AC:

792

AN:

4510

American (AMR)

AF:

0.533

AC:

2869

AN:

5386

Ashkenazi Jewish (ASJ)

AF:

0.518

AC:

1775

AN:

3428

East Asian (EAS)

AF:

0.538

AC:

3483

AN:

6470

South Asian (SAS)

AF:

0.397

AC:

7911

AN:

19952

European-Finnish (FIN)

AF:

0.530

AC:

3459

AN:

6524

Middle Eastern (MID)

AF:

0.519

AC:

276

AN:

532

European-Non Finnish (NFE)

AF:

0.519

AC:

41214

AN:

79366

Other (OTH)

AF:

0.501

AC:

3518

AN:

7016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1503

3006

4508

6011

7514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.424

AC:

64536

AN:

152094

Hom.:

15583

Cov.:

AF XY:

0.426

AC XY:

31691

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.180

AC:

7482

AN:

41500

American (AMR)

AF:

0.519

AC:

7920

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

1877

AN:

3472

East Asian (EAS)

AF:

0.542

AC:

2811

AN:

5182

South Asian (SAS)

AF:

0.417

AC:

2013

AN:

4824

European-Finnish (FIN)

AF:

0.519

AC:

5494

AN:

10580

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.520

AC:

35311

AN:

67958

Other (OTH)

AF:

0.452

AC:

956

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1753

3506

5258

7011

8764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.499

Hom.:

27489

Bravo

AF:

0.416

Asia WGS

AF:

0.465

AC:

1619

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.8

(source)

DANN

Benign

0.39

PhyloP100

1.2

Mutation Taster

=100/0

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over