rs11921705

Variant names:

• chr3-149182812-G-A
• rs11921705
• NM_000096.4:c.2425+654C>T

Variant summary

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

The NM_000096.4(CP):​c.2425+654C>T 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 152,060 control chromosomes in the GnomAD database, including 3,035 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 (3035 hom., cov: 31)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000096.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	NM_000096.4	MANE Select	c.2425+654C>T		intron	N/A	NP_000087.2
	CP	NR_046371.2		n.2249+654C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	ENST00000264613.11	TSL:1 MANE Select	c.2425+654C>T		intron	N/A	ENSP00000264613.6
	CP	ENST00000494544.1	TSL:1	c.1774+654C>T		intron	N/A	ENSP00000420545.1
	CP	ENST00000490639.5	TSL:1	n.2457+654C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22336 AN: 151942 Hom.: 3022 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0655

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0496

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0718

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.147 AC: 22393 AN: 152060 Hom.: 3035 Cov.: 31 AF XY: 0.143 AC XY: 10633 AN XY: 74344

African (AFR) AF: 0.366 AC: 15152 AN: 41424

American (AMR) AF: 0.0737 AC: 1127 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 227 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0320 AC: 154 AN: 4820

European-Finnish (FIN) AF: 0.0496 AC: 524 AN: 10566

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0718 AC: 4883 AN: 68006

Other (OTH) AF: 0.125 AC: 264 AN: 2104

Alfa AF: 0.106 Hom.: 322

Bravo AF: 0.160

Asia WGS AF: 0.0460 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.34
PhyloP100		-0.13
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: rs11921705; hg19: chr3-148900599;