rs11921705

Positions:

• chr3-149182812-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CP	NM_000096.4	c.2425+654C>T		intron_variant		ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.2425+654C>T		intron_variant		1	NM_000096.4	ENSP00000264613	P1
CP	ENST00000494544.1	c.1774+654C>T		intron_variant		1		ENSP00000420545
CP	ENST00000490639.5	n.2457+654C>T		intron_variant, non_coding_transcript_variant		1
CP	ENST00000481169.5	c.2212+654C>T		intron_variant, NMD_transcript_variant		2		ENSP00000418773

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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.0655

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0320

Gnomad4 FIN AF: 0.0496

Gnomad4 NFE AF: 0.0718

Gnomad4 OTH AF: 0.125

Alfa AF: 0.101 Hom.: 285

Bravo AF: 0.160

Asia WGS AF: 0.0460 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs11921705; hg19: chr3-148900599;