rs16861598

chr3-149182259-C-T

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.767

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=-0.86).
• 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_single_submitter, 1 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/exons	MANE	UniProt
CP	NM_000096.4	c.2426-126G>A		intron_variant		ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.2426-126G>A		intron_variant		1	NM_000096.4	P1
CP	ENST00000494544.1	c.1775-126G>A		intron_variant		1
CP	ENST00000490639.5	n.2458-126G>A		intron_variant, non_coding_transcript_variant		1
CP	ENST00000481169.5	c.2213-126G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19402 AN: 152020 Hom.: 3695 Cov.: 31

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

Gnomad4 AFR exome AF: 0.426

Gnomad4 AMR exome AF: 0.0300

Gnomad4 ASJ exome AF: 0.00359

Gnomad4 EAS exome AF: 0.0000578

Gnomad4 SAS exome AF: 0.00680

Gnomad4 FIN exome AF: 0.0205

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.0391

GnomAD4 genome AF: 0.128 AC: 19464 AN: 152136 Hom.: 3708 Cov.: 31 AF XY: 0.124 AC XY: 9201 AN XY: 74408

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.0482

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0241

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.0841

Alfa AF: 0.0351 Hom.: 724

Bravo AF: 0.144

Asia WGS AF: 0.0300 AC: 106 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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.2
Dann	Benign	0.72

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: rs16861598; hg19: chr3-148900046;