rs4974389

Positions:

• chr3-149186136-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000096.4(CP):​c.2077+384C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 285,278 control chromosomes in the GnomAD database, including 32,364 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 0.42 (15583 hom., cov: 33)
  • Exomes 𝑓: 0.49 (16781 hom.)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CP	NM_000096.4	c.2077+384C>T		intron_variant		ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.2077+384C>T		intron_variant		1	NM_000096.4	ENSP00000264613.6

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64529 AN: 151976 Hom.: 15579 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.490 AC: 65297 AN: 133184 Hom.: 16781 Cov.: 0 AF XY: 0.479 AC XY: 33816 AN XY: 70564

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.533

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.397

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.424 AC: 64536 AN: 152094 Hom.: 15583 Cov.: 33 AF XY: 0.426 AC XY: 31691 AN XY: 74372

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.541

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.452

Alfa AF: 0.503 Hom.: 23344

Bravo AF: 0.416

Asia WGS AF: 0.465 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.8
DANN	Benign	0.39

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: rs4974389; hg19: chr3-148903923;