chr3-149197841-T-C

Variant names:

• chr3-149197841-T-C
• rs13075921
• NM_000096.4:c.1713+526A>G

Variant summary

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

The NM_000096.4(CP):​c.1713+526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,234 control chromosomes in the GnomAD database, including 713 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 0.091 (713 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.1713+526A>G		intron_variant	Intron 9 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.1713+526A>G		intron_variant	Intron 9 of 18	1	NM_000096.4	ENSP00000264613.6

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13903 AN: 152116 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0637

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.0536

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0914 AC: 13907 AN: 152234 Hom.: 713 Cov.: 32 AF XY: 0.0894 AC XY: 6655 AN XY: 74440

African (AFR) AF: 0.0888 AC: 3690 AN: 41544

American (AMR) AF: 0.0636 AC: 973 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3472

East Asian (EAS) AF: 0.0364 AC: 189 AN: 5188

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4826

European-Finnish (FIN) AF: 0.0918 AC: 972 AN: 10584

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7213 AN: 68012

Other (OTH) AF: 0.107 AC: 227 AN: 2112

Alfa AF: 0.0213 Hom.: 149

Bravo AF: 0.0894

Asia WGS AF: 0.0760 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.40
PhyloP100		-0.48
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: rs13075921; hg19: chr3-148915628;