chr3-149207738-T-C

Variant names:

• chr3-149207738-T-C
• rs1523515
• NM_000096.4:c.782-121A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000096.4(CP):​c.782-121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 1,032,536 control chromosomes in the GnomAD database, including 463,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (68701 hom., cov: 31)
  • Exomes 𝑓: 0.95 (394439 hom.)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.915

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-149207738-T-C is Benign according to our data. Variant chr3-149207738-T-C is described in ClinVar as [Benign]. Clinvar id is 1265279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.782-121A>G		intron_variant	Intron 4 of 18	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.782-121A>G		intron_variant	Intron 4 of 18	1	NM_000096.4	ENSP00000264613.6

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144477 AN: 152114 Hom.: 68645 Cov.: 31

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.969

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.956

GnomAD4 exome AF: 0.946 AC: 832945 AN: 880304 Hom.: 394439 AF XY: 0.943 AC XY: 431242 AN XY: 457328

Gnomad4 AFR exome AF: 0.947

Gnomad4 AMR exome AF: 0.970

Gnomad4 ASJ exome AF: 0.942

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.878

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.950

Gnomad4 OTH exome AF: 0.948

GnomAD4 genome AF: 0.950 AC: 144592 AN: 152232 Hom.: 68701 Cov.: 31 AF XY: 0.948 AC XY: 70563 AN XY: 74434

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.969

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.950

Gnomad4 OTH AF: 0.957

Alfa AF: 0.944 Hom.: 30034

Bravo AF: 0.954

Asia WGS AF: 0.953 AC: 3314 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.85

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: rs1523515; hg19: chr3-148925525;