rs6799507

Positions:

• chr3-149188240-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000096.4(CP):​c.1714-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,571,166 control chromosomes in the GnomAD database, including 5,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2967 hom., cov: 31)
  • Exomes 𝑓: 0.023 (2786 hom.)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.329

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-149188240-A-G is Benign according to our data. Variant chr3-149188240-A-G is described in ClinVar as [Benign]. Clinvar id is 1232102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CP	NM_000096.4	c.1714-38T>C		intron_variant		ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.1714-38T>C		intron_variant		1	NM_000096.4	ENSP00000264613	P1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17544 AN: 152062 Hom.: 2952 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0833

GnomAD3 exomes AF: 0.0375 AC: 9149 AN: 244298 Hom.: 1231 AF XY: 0.0302 AC XY: 3998 AN XY: 132532

Gnomad AFR exome AF: 0.392

Gnomad AMR exome AF: 0.0222

Gnomad ASJ exome AF: 0.00513

Gnomad EAS exome AF: 0.0000548

Gnomad SAS exome AF: 0.00734

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.0292

GnomAD4 exome AF: 0.0226 AC: 32103 AN: 1418984 Hom.: 2786 Cov.: 25 AF XY: 0.0209 AC XY: 14820 AN XY: 708396

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.00578

Gnomad4 EAS exome AF: 0.0000508

Gnomad4 SAS exome AF: 0.00703

Gnomad4 FIN exome AF: 0.0209

Gnomad4 NFE exome AF: 0.0130

Gnomad4 OTH exome AF: 0.0355

GnomAD4 genome AF: 0.116 AC: 17609 AN: 152182 Hom.: 2967 Cov.: 31 AF XY: 0.113 AC XY: 8402 AN XY: 74424

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00766

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.0843

Alfa AF: 0.0277 Hom.: 567

Bravo AF: 0.130

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.76

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: rs6799507; hg19: chr3-148906027;