3-149221163-A-G

Variant names:

• chr3-149221163-A-G
• rs7652826
• NM_000096.4:c.146+484T>C

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+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 NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988
• Publications: 8 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=-0.82).
• 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 rank	MANE	Protein	UniProt
CP	NM_000096.4	c.146+484T>C		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+484T>C		intron_variant	Intron 1 of 18	1	NM_000096.4	ENSP00000264613.6

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

African (AFR) AF: 0.157 AC: 6511 AN: 41494

American (AMR) AF: 0.568 AC: 8679 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2162 AN: 3466

East Asian (EAS) AF: 0.603 AC: 3124 AN: 5178

South Asian (SAS) AF: 0.435 AC: 2101 AN: 4826

European-Finnish (FIN) AF: 0.526 AC: 5549 AN: 10554

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.542 AC: 36799 AN: 67942

Other (OTH) AF: 0.483 AC: 1022 AN: 2116

Alfa AF: 0.517 Hom.: 63577

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
PhyloP100		0.99
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: rs7652826; hg19: chr3-148938950;