rs11709714

chr3-149214193-G-Achr3-149214193-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000096.4(CP):c.147-1495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,948 control chromosomes in the GnomAD database, including 13,723 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (13723 hom., cov: 31)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CP	NM_000096.4	c.147-1495C>T		intron_variant		ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.147-1495C>T		intron_variant		1	NM_000096.4	P1
CP	ENST00000490639.5	n.179-1495C>T		intron_variant, non_coding_transcript_variant		1
CP	ENST00000455472.3	c.267-1495C>T		intron_variant		5
CP	ENST00000481169.5	c.147-1495C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60381 AN: 151830 Hom.: 13718 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.397 AC: 60395 AN: 151948 Hom.: 13723 Cov.: 31 AF XY: 0.399 AC XY: 29646 AN XY: 74274

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.433

Alfa AF: 0.468 Hom.: 12983

Bravo AF: 0.395

Asia WGS AF: 0.473 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.1
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11709714; hg19: chr3-148931980;