3-149207738-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, Ambry Genetics, Orphanet
• disorder of iron metabolism and transport

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000096.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	NM_000096.4	MANE Select	c.782-121A>G		intron	N/A	NP_000087.2	P00450
	CP	NR_046371.2		n.819-121A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CP	ENST00000264613.11	TSL:1 MANE Select	c.782-121A>G		intron	N/A	ENSP00000264613.6	P00450
	CP	ENST00000494544.1	TSL:1	c.131-121A>G		intron	N/A	ENSP00000420545.1	H7C5R1
	CP	ENST00000490639.5	TSL:1	n.814-121A>G		intron	N/A

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

African (AFR) AF: 0.947 AC: 20695 AN: 21854

American (AMR) AF: 0.970 AC: 37601 AN: 38772

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 20872 AN: 22150

East Asian (EAS) AF: 1.00 AC: 35020 AN: 35026

South Asian (SAS) AF: 0.878 AC: 61964 AN: 70536

European-Finnish (FIN) AF: 0.947 AC: 39653 AN: 41872

Middle Eastern (MID) AF: 0.916 AC: 3697 AN: 4036

European-Non Finnish (NFE) AF: 0.950 AC: 574481 AN: 604974

Other (OTH) AF: 0.948 AC: 38962 AN: 41084

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

African (AFR) AF: 0.947 AC: 39332 AN: 41548

American (AMR) AF: 0.969 AC: 14812 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3257 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5166 AN: 5170

South Asian (SAS) AF: 0.884 AC: 4262 AN: 4820

European-Finnish (FIN) AF: 0.946 AC: 10045 AN: 10618

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64572 AN: 68006

Other (OTH) AF: 0.957 AC: 2020 AN: 2110

Alfa AF: 0.947 Hom.: 44954

Bravo AF: 0.954

Asia WGS AF: 0.953 AC: 3314 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.85
PhyloP100		-0.92
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: rs1523515; hg19: chr3-148925525;