chr3-149187220-T-A

Variant names:

• chr3-149187220-T-A
• rs701754
• NM_000096.4:c.1865-488A>T

Variant summary

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

The NM_000096.4(CP):​c.1865-488A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,198 control chromosomes in the GnomAD database, including 53,006 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 0.83 (53006 hom., cov: 31)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics, Orphanet
• disorder of iron metabolism and transport

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000096.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	NM_000096.4	MANE Select	c.1865-488A>T		intron	N/A	NP_000087.2	P00450
	CP	NR_046371.2		n.1901+832A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	ENST00000264613.11	TSL:1 MANE Select	c.1865-488A>T		intron	N/A	ENSP00000264613.6	P00450
	CP	ENST00000494544.1	TSL:1	c.1214-488A>T		intron	N/A	ENSP00000420545.1	H7C5R1
	CP	ENST00000489736.5	TSL:1	n.1090-488A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126593 AN: 152080 Hom.: 52952 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.839

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

GnomAD4 genome AF: 0.832 AC: 126704 AN: 152198 Hom.: 53006 Cov.: 31 AF XY: 0.825 AC XY: 61365 AN XY: 74408

African (AFR) AF: 0.869 AC: 36070 AN: 41518

American (AMR) AF: 0.814 AC: 12445 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2818 AN: 3470

East Asian (EAS) AF: 0.587 AC: 3038 AN: 5176

South Asian (SAS) AF: 0.712 AC: 3438 AN: 4826

European-Finnish (FIN) AF: 0.799 AC: 8459 AN: 10584

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57662 AN: 68004

Other (OTH) AF: 0.840 AC: 1777 AN: 2116

Alfa AF: 0.839 Hom.: 6724

Bravo AF: 0.836

Asia WGS AF: 0.692 AC: 2408 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		0.14
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: rs701754; hg19: chr3-148905007;