rs17787768

chr3-149177744-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000096.4(CP):c.3018+96C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 1,361,656 control chromosomes in the GnomAD database, including 6,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (467 hom., cov: 32)
  • Exomes 𝑓: 0.089 (5826 hom.)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0900

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-149177744-G-C is Benign according to our data. Variant chr3-149177744-G-C is described in ClinVar as [Benign]. Clinvar id is 1257508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CP	NM_000096.4	c.3018+96C>G		intron_variant		ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.3018+96C>G		intron_variant		1	NM_000096.4	P1

Frequencies

GnomAD3 genomes AF: 0.0644 AC: 9795 AN: 152070 Hom.: 465 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.0664

GnomAD4 exome AF: 0.0889 AC: 107510 AN: 1209468 Hom.: 5826 Cov.: 17 AF XY: 0.0932 AC XY: 57177 AN XY: 613716

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.0390

Gnomad4 ASJ exome AF: 0.0789

Gnomad4 EAS exome AF: 0.00484

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.0473

Gnomad4 NFE exome AF: 0.0902

Gnomad4 OTH exome AF: 0.0836

GnomAD4 genome AF: 0.0644 AC: 9799 AN: 152188 Hom.: 467 Cov.: 32 AF XY: 0.0648 AC XY: 4822 AN XY: 74416

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.00829

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.0700

Alfa AF: 0.0746 Hom.: 57

Bravo AF: 0.0578

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.48
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs17787768; hg19: chr3-148895531;