rs6799507

Variant names:

• chr3-149188240-A-G
• rs6799507
• NM_000096.4:c.1714-38T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000096.4(CP):​c.1714-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,571,166 control chromosomes in the GnomAD database, including 5,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2967 hom., cov: 31)
  • Exomes 𝑓: 0.023 (2786 hom.)
• Consequence: CP NM_000096.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.329
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-149188240-A-G is Benign according to our data. Variant chr3-149188240-A-G is described in ClinVar as Benign. ClinVar VariationId is 1232102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CP	NM_000096.4	c.1714-38T>C		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.1714-38T>C		intron_variant	Intron 9 of 18	1	NM_000096.4	ENSP00000264613.6

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17544 AN: 152062 Hom.: 2952 Cov.: 31

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00807

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0833

GnomAD2 exomes AF: 0.0375 AC: 9149 AN: 244298 AF XY: 0.0302

Gnomad AFR exome AF: 0.392

Gnomad AMR exome AF: 0.0222

Gnomad ASJ exome AF: 0.00513

Gnomad EAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.0228

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.0292

GnomAD4 exome AF: 0.0226 AC: 32103 AN: 1418984 Hom.: 2786 Cov.: 25 AF XY: 0.0209 AC XY: 14820 AN XY: 708396

African (AFR) AF: 0.396 AC: 12896 AN: 32548

American (AMR) AF: 0.0259 AC: 1145 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.00578 AC: 149 AN: 25776

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39360

South Asian (SAS) AF: 0.00703 AC: 599 AN: 85204

European-Finnish (FIN) AF: 0.0209 AC: 1000 AN: 47748

Middle Eastern (MID) AF: 0.0370 AC: 210 AN: 5676

European-Non Finnish (NFE) AF: 0.0130 AC: 14002 AN: 1079304

Other (OTH) AF: 0.0355 AC: 2100 AN: 59076

GnomAD4 genome AF: 0.116 AC: 17609 AN: 152182 Hom.: 2967 Cov.: 31 AF XY: 0.113 AC XY: 8402 AN XY: 74424

African (AFR) AF: 0.377 AC: 15608 AN: 41444

American (AMR) AF: 0.0439 AC: 672 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00766 AC: 37 AN: 4828

European-Finnish (FIN) AF: 0.0240 AC: 255 AN: 10616

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 817 AN: 68016

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0383 Hom.: 1165

Bravo AF: 0.130

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 10, 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	-0.84
CADD	Benign	5.8
DANN	Benign	0.76
PhyloP100		-0.33
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: rs6799507; hg19: chr3-148906027;