chr3-149183207-C-A

Variant names:

• chr3-149183207-C-A
• rs11714000
• NM_000096.4:c.2425+259G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000096.4(CP):​c.2425+259G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,928 control chromosomes in the GnomAD database, including 3,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (3011 hom., cov: 31)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.241
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-149183207-C-A is Benign according to our data. Variant chr3-149183207-C-A is described in ClinVar as Benign. ClinVar VariationId is 1274534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.2425+259G>T		intron_variant	Intron 13 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.2425+259G>T		intron_variant	Intron 13 of 18	1	NM_000096.4	ENSP00000264613.6
CP	ENST00000494544.1	c.1774+259G>T		intron_variant	Intron 10 of 15	1		ENSP00000420545.1
CP	ENST00000490639.5	n.2457+259G>T		intron_variant	Intron 13 of 16	1
CP	ENST00000481169.5	n.2212+259G>T		intron_variant	Intron 12 of 17	2		ENSP00000418773.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22661 AN: 151810 Hom.: 2998 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0807

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0318

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.150 AC: 22717 AN: 151928 Hom.: 3011 Cov.: 31 AF XY: 0.145 AC XY: 10798 AN XY: 74258

African (AFR) AF: 0.362 AC: 14954 AN: 41350

American (AMR) AF: 0.0805 AC: 1231 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 230 AN: 3466

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0314 AC: 151 AN: 4810

European-Finnish (FIN) AF: 0.0513 AC: 541 AN: 10538

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5268 AN: 67976

Other (OTH) AF: 0.131 AC: 277 AN: 2108

Alfa AF: 0.129 Hom.: 277

Bravo AF: 0.163

Asia WGS AF: 0.0470 AC: 168 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.81
CADD	Benign	4.4
DANN	Benign	0.38
PhyloP100		0.24
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

Other links and lift over

dbSNP: rs11714000; hg19: chr3-148900994;