rs16861579

Variant names:

• chr3-149177339-A-G
• rs16861579
• NM_000096.4:c.3018+501T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000096.4(CP):​c.3018+501T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,156 control chromosomes in the GnomAD database, including 2,206 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 0.15 (2206 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.3018+501T>C		intron_variant	Intron 17 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.3018+501T>C		intron_variant	Intron 17 of 18	1	NM_000096.4	ENSP00000264613.6

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22413 AN: 152036 Hom.: 2208 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.147 AC: 22415 AN: 152156 Hom.: 2206 Cov.: 32 AF XY: 0.152 AC XY: 11329 AN XY: 74374

African (AFR) AF: 0.0380 AC: 1579 AN: 41558

American (AMR) AF: 0.127 AC: 1934 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3468

East Asian (EAS) AF: 0.281 AC: 1447 AN: 5158

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4820

European-Finnish (FIN) AF: 0.275 AC: 2907 AN: 10572

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12600 AN: 67976

Other (OTH) AF: 0.125 AC: 264 AN: 2116

Alfa AF: 0.167 Hom.: 407

Bravo AF: 0.131

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		-0.71
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: rs16861579; hg19: chr3-148895126;