rs3816893

Variant names:

• chr3-149209924-A-T
• rs3816893
• NM_000096.4:c.607+243T>A

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.607+243T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0874 in 152,208 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.087 (634 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.769
• Publications: 9 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=-0.94).
• BP6: Variant 3-149209924-A-T is Benign according to our data. Variant chr3-149209924-A-T is described in ClinVar as Benign. ClinVar VariationId is 1297814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.607+243T>A		intron_variant	Intron 3 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.607+243T>A		intron_variant	Intron 3 of 18	1	NM_000096.4	ENSP00000264613.6
CP	ENST00000490639.5	n.639+243T>A		intron_variant	Intron 3 of 16	1
CP	ENST00000481169.5	n.607+243T>A		intron_variant	Intron 3 of 17	2		ENSP00000418773.1

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13305 AN: 152090 Hom.: 633 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0378

Gnomad SAS AF: 0.0548

Gnomad FIN AF: 0.0903

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.0874 AC: 13310 AN: 152208 Hom.: 634 Cov.: 32 AF XY: 0.0862 AC XY: 6418 AN XY: 74418

African (AFR) AF: 0.0854 AC: 3547 AN: 41540

American (AMR) AF: 0.0625 AC: 956 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3470

East Asian (EAS) AF: 0.0373 AC: 193 AN: 5180

South Asian (SAS) AF: 0.0550 AC: 265 AN: 4816

European-Finnish (FIN) AF: 0.0903 AC: 958 AN: 10606

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0987 AC: 6711 AN: 67982

Other (OTH) AF: 0.105 AC: 223 AN: 2116

Alfa AF: 0.0926 Hom.: 91

Bravo AF: 0.0864

Asia WGS AF: 0.0720 AC: 252 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	-0.94
CADD	Benign	0.16
DANN	Benign	0.44
PhyloP100		-0.77
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: rs3816893; hg19: chr3-148927711;