3-149220559-T-C

Variant names:

• chr3-149220559-T-C
• rs1879169
• NM_000096.4:c.146+1088A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000096.4(CP):​c.146+1088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,078 control chromosomes in the GnomAD database, including 1,022 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 0.10 (1022 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.761
• Publications: 4 publications found

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]

CP Gene-Disease associations (from GenCC):

• aceruloplasminemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• disorder of iron metabolism and transport

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000286714 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.146+1088A>G		intron_variant	Intron 1 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.146+1088A>G		intron_variant	Intron 1 of 18	1	NM_000096.4	ENSP00000264613.6

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15254 AN: 151960 Hom.: 1020 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.100 AC: 15268 AN: 152078 Hom.: 1022 Cov.: 32 AF XY: 0.106 AC XY: 7886 AN XY: 74330

African (AFR) AF: 0.0396 AC: 1646 AN: 41548

American (AMR) AF: 0.150 AC: 2285 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1494 AN: 5174

South Asian (SAS) AF: 0.167 AC: 805 AN: 4828

European-Finnish (FIN) AF: 0.152 AC: 1592 AN: 10488

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6849 AN: 67984

Other (OTH) AF: 0.111 AC: 235 AN: 2108

Alfa AF: 0.101 Hom.: 143

Bravo AF: 0.0984

Asia WGS AF: 0.200 AC: 684 AN: 3432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.0
DANN	Benign	0.54
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1879169; hg19: chr3-148938346;