rs772908

Variant names:

• chr3-149205869-G-A
• rs772908
• NM_000096.4:c.1208+299C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000096.4(CP):​c.1208+299C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,048 control chromosomes in the GnomAD database, including 4,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4022 hom., cov: 31)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.107
• Publications: 6 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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• disorder of iron metabolism and transport

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-149205869-G-A is Benign according to our data. Variant chr3-149205869-G-A is described in ClinVar as [Benign]. Clinvar id is 1242928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.1208+299C>T		intron_variant	Intron 6 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.1208+299C>T		intron_variant	Intron 6 of 18	1	NM_000096.4	ENSP00000264613.6

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34042 AN: 151930 Hom.: 4019 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.224 AC: 34063 AN: 152048 Hom.: 4022 Cov.: 31 AF XY: 0.220 AC XY: 16366 AN XY: 74308

African (AFR) AF: 0.194 AC: 8056 AN: 41474

American (AMR) AF: 0.200 AC: 3062 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3468

East Asian (EAS) AF: 0.0202 AC: 105 AN: 5186

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4814

European-Finnish (FIN) AF: 0.234 AC: 2472 AN: 10564

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17686 AN: 67942

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.242 Hom.: 12357

Bravo AF: 0.217

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.71
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs772908; hg19: chr3-148923656;