rs773050

Positions:

• chr3-149195209-G-A
• chr3-149195209-G-T

Variant summary

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

The NM_000096.4(CP):​c.1713+3158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,268 control chromosomes in the GnomAD database, including 63,731 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 0.91 (63731 hom., cov: 33)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CP	NM_000096.4	c.1713+3158C>T		intron_variant		ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.1713+3158C>T		intron_variant		1	NM_000096.4	ENSP00000264613	P1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138890 AN: 152150 Hom.: 63689 Cov.: 33

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.913 AC: 138991 AN: 152268 Hom.: 63731 Cov.: 33 AF XY: 0.914 AC XY: 68024 AN XY: 74462

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.953

Gnomad4 ASJ AF: 0.937

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.967

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.937

Alfa AF: 0.938 Hom.: 62656

Bravo AF: 0.911

Asia WGS AF: 0.947 AC: 3289 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.71
DANN	Benign	0.43

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: rs773050; hg19: chr3-148912996;