rs13075921

chr3-149197841-T-C

Variant summary

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

The NM_000096.4(CP):c.1713+526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,234 control chromosomes in the GnomAD database, including 713 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 0.091 (713 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CP	NM_000096.4	c.1713+526A>G		intron_variant		ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.1713+526A>G		intron_variant		1	NM_000096.4	P1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13903 AN: 152116 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0914 AC: 13907 AN: 152234 Hom.: 713 Cov.: 32 AF XY: 0.0894 AC XY: 6655 AN XY: 74440

Gnomad4 AFR AF: 0.0888

Gnomad4 AMR AF: 0.0636

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.0364

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0237 Hom.: 145

Bravo AF: 0.0894

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.9
Dann	Benign	0.40

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: rs13075921; hg19: chr3-148915628;