3-149194160-G-C

Position:

• chr3-149194160-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CP	NM_000096.4	c.1713+4207C>G		intron_variant		ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.1713+4207C>G		intron_variant		1	NM_000096.4	P1

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

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0279

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.0437

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.85

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: rs9853335; hg19: chr3-148911947;