NM_000096.4:c.147-1495C>T

Variant names:

• chr3-149214193-G-A
• rs11709714
• NM_000096.4:c.147-1495C>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.147-1495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,948 control chromosomes in the GnomAD database, including 13,723 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 0.40 (13723 hom., cov: 31)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.147-1495C>T		intron_variant	Intron 1 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.147-1495C>T		intron_variant	Intron 1 of 18	1	NM_000096.4	ENSP00000264613.6
CP	ENST00000490639.5	n.179-1495C>T		intron_variant	Intron 1 of 16	1
CP	ENST00000455472.3	c.267-1495C>T		intron_variant	Intron 2 of 3	5		ENSP00000426888.1
CP	ENST00000481169.5	n.147-1495C>T		intron_variant	Intron 1 of 17	2		ENSP00000418773.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60381 AN: 151830 Hom.: 13718 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.397 AC: 60395 AN: 151948 Hom.: 13723 Cov.: 31 AF XY: 0.399 AC XY: 29646 AN XY: 74274

African (AFR) AF: 0.157 AC: 6511 AN: 41462

American (AMR) AF: 0.534 AC: 8161 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1991 AN: 3472

East Asian (EAS) AF: 0.516 AC: 2658 AN: 5148

South Asian (SAS) AF: 0.413 AC: 1981 AN: 4800

European-Finnish (FIN) AF: 0.469 AC: 4954 AN: 10560

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32602 AN: 67912

Other (OTH) AF: 0.433 AC: 914 AN: 2110

Alfa AF: 0.457 Hom.: 16535

Bravo AF: 0.395

Asia WGS AF: 0.473 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11709714; hg19: chr3-148931980;