chr3-149195209-G-A

Variant summary

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

The NM_000096.4(CP):​c.1713+3158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,268 control chromosomes in the GnomAD database, including 63,731 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 0.91 ( 63731 hom., cov: 33)

Consequence

CP
NM_000096.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.567

Publications

4 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

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=-0.99).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPNM_000096.4 linkc.1713+3158C>T intron_variant Intron 9 of 18 ENST00000264613.11 NP_000087.2 P00450A5PL27

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPENST00000264613.11 linkc.1713+3158C>T intron_variant Intron 9 of 18 1 NM_000096.4 ENSP00000264613.6 P00450

Frequencies

GnomAD3 genomes
AF:
0.913
AC:
138890
AN:
152150
Hom.:
63689
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.816
Gnomad AMI
AF:
0.942
Gnomad AMR
AF:
0.953
Gnomad ASJ
AF:
0.937
Gnomad EAS
AF:
0.999
Gnomad SAS
AF:
0.887
Gnomad FIN
AF:
0.967
Gnomad MID
AF:
0.899
Gnomad NFE
AF:
0.947
Gnomad OTH
AF:
0.935
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.913
AC:
138991
AN:
152268
Hom.:
63731
Cov.:
33
AF XY:
0.914
AC XY:
68024
AN XY:
74462
show subpopulations
African (AFR)
AF:
0.816
AC:
33890
AN:
41530
American (AMR)
AF:
0.953
AC:
14571
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.937
AC:
3252
AN:
3472
East Asian (EAS)
AF:
0.999
AC:
5182
AN:
5186
South Asian (SAS)
AF:
0.886
AC:
4278
AN:
4826
European-Finnish (FIN)
AF:
0.967
AC:
10257
AN:
10612
Middle Eastern (MID)
AF:
0.898
AC:
264
AN:
294
European-Non Finnish (NFE)
AF:
0.947
AC:
64460
AN:
68034
Other (OTH)
AF:
0.937
AC:
1980
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
587
1174
1760
2347
2934
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
902
1804
2706
3608
4510
<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:
0.935
Hom.:
93385
Bravo
AF:
0.911
Asia WGS
AF:
0.947
AC:
3289
AN:
3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
0.71
DANN
Benign
0.43
PhyloP100
-0.57
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

Other links and lift over

dbSNP: rs773050; hg19: chr3-148912996; API