rs11714000

chr3-149183207-C-A

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.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

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=-0.81).
• BP6: Variant 3-149183207-C-A is Benign according to our data. Variant chr3-149183207-C-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
CP	NM_000096.4	c.2425+259G>T		intron_variant		ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.2425+259G>T		intron_variant		1	NM_000096.4	P1
CP	ENST00000494544.1	c.1774+259G>T		intron_variant		1
CP	ENST00000490639.5	n.2457+259G>T		intron_variant, non_coding_transcript_variant		1
CP	ENST00000481169.5	c.2212+259G>T		intron_variant, NMD_transcript_variant		2

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

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.0805

Gnomad4 ASJ AF: 0.0664

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0314

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.131

Alfa AF: 0.121 Hom.: 238

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

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	-0.81
Cadd	Benign	4.4
Dann	Benign	0.38

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: rs11714000; hg19: chr3-148900994;