rs17838831

Variant names:

• chr3-149222074-T-C
• rs17838831
• NM_000096.4:c.-282A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000096.4(CP):​c.-282A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 370,016 control chromosomes in the GnomAD database, including 5,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2158 hom., cov: 32)
  • Exomes 𝑓: 0.16 (3258 hom.)
• Consequence: CP NM_000096.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-149222074-T-C is Benign according to our data. Variant chr3-149222074-T-C is described in ClinVar as [Benign]. Clinvar id is 1293787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.-282A>G		upstream_gene_variant		ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.-282A>G		upstream_gene_variant		1	NM_000096.4	ENSP00000264613.6
CP	ENST00000490639.5	n.-250A>G		upstream_gene_variant		1
CP	ENST00000455472.3	c.-282A>G		upstream_gene_variant		5		ENSP00000426888.1
CP	ENST00000481169.5	n.-282A>G		upstream_gene_variant		2		ENSP00000418773.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24882 AN: 152058 Hom.: 2151 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0960

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.180 AC: 8277 AN: 45908 Hom.: 930 AF XY: 0.182 AC XY: 4275 AN XY: 23530

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.190

Gnomad ASJ exome AF: 0.0850

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.200

Gnomad FIN exome AF: 0.184

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.161 AC: 35099 AN: 217840 Hom.: 3258 Cov.: 0 AF XY: 0.163 AC XY: 19014 AN XY: 116342

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.0997

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.140

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.164 AC: 24915 AN: 152176 Hom.: 2158 Cov.: 32 AF XY: 0.167 AC XY: 12404 AN XY: 74394

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0960

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.169

Alfa AF: 0.144 Hom.: 1706

Bravo AF: 0.165

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 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	-0.89
CADD	Benign	1.0
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17838831; hg19: chr3-148939861;