rs701755

Positions:

• chr3-149184927-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000096.4(CP):​c.2285+312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,228 control chromosomes in the GnomAD database, including 2,115 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 0.16 (2115 hom., cov: 32)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CP	NM_000096.4	c.2285+312A>G		intron_variant		ENST00000264613.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CP	ENST00000264613.11	c.2285+312A>G		intron_variant		1	NM_000096.4	P1
CP	ENST00000494544.1	c.1634+312A>G		intron_variant		1
CP	ENST00000490639.5	n.2317+312A>G		intron_variant, non_coding_transcript_variant		1
CP	ENST00000481169.5	c.2072+312A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24433 AN: 152110 Hom.: 2112 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.161 AC: 24452 AN: 152228 Hom.: 2115 Cov.: 32 AF XY: 0.158 AC XY: 11736 AN XY: 74434

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.00945

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.167

Alfa AF: 0.185 Hom.: 3753

Bravo AF: 0.154

Asia WGS AF: 0.0910 AC: 316 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.59

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: rs701755; hg19: chr3-148902714;