3-149221163-A-G

Position:

• chr3-149221163-A-G

Variant summary

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

The ENST00000264613.11(CP):​c.146+484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,050 control chromosomes in the GnomAD database, including 16,856 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 0.44 (16856 hom., cov: 32)
• Consequence: CP ENST00000264613.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CP	NM_000096.4	c.146+484T>C		intron_variant		ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.146+484T>C		intron_variant		1	NM_000096.4	ENSP00000264613	P1
CP	ENST00000490639.5	n.178+484T>C		intron_variant, non_coding_transcript_variant		1
CP	ENST00000455472.3	c.146+484T>C		intron_variant		5		ENSP00000426888
CP	ENST00000481169.5	c.146+484T>C		intron_variant, NMD_transcript_variant		2		ENSP00000418773

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66569 AN: 151932 Hom.: 16855 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.438 AC: 66577 AN: 152050 Hom.: 16856 Cov.: 32 AF XY: 0.440 AC XY: 32672 AN XY: 74326

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.483

Alfa AF: 0.533 Hom.: 28429

Bravo AF: 0.433

Asia WGS AF: 0.516 AC: 1795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.53

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: rs7652826; hg19: chr3-148938950;