ENST00000790417.1:n.33+2119T>C

Variant names:

• chr3-149222074-T-C
• rs17838831
• ENST00000790417.1:n.33+2119T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000790417.1(ENSG00000286714):​n.33+2119T>C variant causes a intron 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: ENSG00000286714 ENST00000790417.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.03
• Publications: 15 publications found

Genes affected

ENSG00000286714 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000790417.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	NM_000096.4	MANE Select	c.-282A>G		upstream_gene	N/A	NP_000087.2
	CP	NR_046371.2		n.-245A>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286714	ENST00000790417.1		n.33+2119T>C		intron	N/A
	ENSG00000286714	ENST00000790423.1		n.92-2923T>C		intron	N/A
	ENSG00000286714	ENST00000790424.1		n.142-3275T>C		intron	N/A

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

GnomAD2 exomes AF: 0.180 AC: 8277 AN: 45908 AF XY: 0.182

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 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

African (AFR) AF: 0.153 AC: 1089 AN: 7096

American (AMR) AF: 0.196 AC: 1844 AN: 9394

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 640 AN: 6418

East Asian (EAS) AF: 0.319 AC: 3976 AN: 12472

South Asian (SAS) AF: 0.188 AC: 5144 AN: 27412

European-Finnish (FIN) AF: 0.180 AC: 1743 AN: 9688

Middle Eastern (MID) AF: 0.115 AC: 103 AN: 898

European-Non Finnish (NFE) AF: 0.140 AC: 18533 AN: 132080

Other (OTH) AF: 0.164 AC: 2027 AN: 12382

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

African (AFR) AF: 0.163 AC: 6769 AN: 41510

American (AMR) AF: 0.183 AC: 2792 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0960 AC: 333 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1699 AN: 5176

South Asian (SAS) AF: 0.201 AC: 969 AN: 4822

European-Finnish (FIN) AF: 0.187 AC: 1979 AN: 10598

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9791 AN: 68002

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.146 Hom.: 2270

Bravo AF: 0.165

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-1.0
PromoterAI		-0.058	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs17838831; hg19: chr3-148939861;