3-149194160-G-C

Variant names:

• chr3-149194160-G-C
• rs9853335
• NM_000096.4:c.1713+4207C>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.1713+4207C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 151,602 control chromosomes in the GnomAD database, including 469 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 0.065 (469 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0937 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.1713+4207C>G		intron	N/A	NP_000087.2	P00450
	CP	NR_046371.2		n.1750+4207C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	ENST00000264613.11	TSL:1 MANE Select	c.1713+4207C>G		intron	N/A	ENSP00000264613.6	P00450
	CP	ENST00000494544.1	TSL:1	c.1062+4207C>G		intron	N/A	ENSP00000420545.1	H7C5R1
	CP	ENST00000489736.5	TSL:1	n.938+4207C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9786 AN: 151486 Hom.: 469 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.0947

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0956

Gnomad OTH AF: 0.0441

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

GnomAD4 genome AF: 0.0645 AC: 9785 AN: 151602 Hom.: 469 Cov.: 32 AF XY: 0.0650 AC XY: 4813 AN XY: 74064

African (AFR) AF: 0.0148 AC: 612 AN: 41328

American (AMR) AF: 0.0367 AC: 559 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 117 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0279 AC: 134 AN: 4798

European-Finnish (FIN) AF: 0.162 AC: 1686 AN: 10412

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0957 AC: 6495 AN: 67902

Other (OTH) AF: 0.0437 AC: 92 AN: 2106

Alfa AF: 0.0801 Hom.: 86

Bravo AF: 0.0521

Asia WGS AF: 0.0150 AC: 51 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.85
PhyloP100		1.3
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: rs9853335; hg19: chr3-148911947;