Variant chr19-16896552-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015692.5(CPAMD8):c.5179G>A(p.Asp1727Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,502,024 control chromosomes in the GnomAD database, including 535 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 261 hom., cov: 31)

Exomes 𝑓: 0.0056 ( 274 hom. )

Consequence

CPAMD8
NM_015692.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.932

Variant links:

Genes affected

CPAMD8 (HGNC:23228): (C3 and PZP like alpha-2-macroglobulin domain containing 8) This gene encodes a member of the protease inhibitor I39 (alpha-2-macroglobulin) family of proteins. These proteins are important in innate and acquired immunity. The encoded protein is membrane-associated and proteolytically processed to generate two chains. Mutations in this gene cause a form of anterior segment dysgenesis, a developmental disorder of the eye. [provided by RefSeq, May 2017]

CPAMD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016382039).

BP6

Variant 19-16896552-C-T is Benign according to our data. Variant chr19-16896552-C-T is described in ClinVar as [Benign]. Clinvar id is 1248916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-16896552-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPAMD8	NM_015692.5 linkuse as main transcript	c.5179G>A	p.Asp1727Asn	missense_variant	40/42	ENST00000443236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPAMD8	ENST00000443236.7 linkuse as main transcript	c.5179G>A	p.Asp1727Asn	missense_variant	40/42	1	NM_015692.5	P2	Q8IZJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5296

AN:

152104

Hom.:

259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0523

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0137

AC:

1404

AN:

102614

Hom.:

AF XY:

0.0121

AC XY:

689

AN XY:

57048

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.0661

Gnomad SAS exome

AF:

0.00409

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00188

Gnomad OTH exome

AF:

0.00866

GnomAD4 exome

AF:

0.00558

AC:

7533

AN:

1349812

Hom.:

274

Cov.:

AF XY:

0.00516

AC XY:

3432

AN XY:

665168

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.0126

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.0444

Gnomad4 SAS exome

AF:

0.00427

Gnomad4 FIN exome

AF:

0.0000304

Gnomad4 NFE exome

AF:

0.000677

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.0349

AC:

5308

AN:

152212

Hom.:

261

Cov.:

AF XY:

0.0335

AC XY:

2492

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.108

Gnomad4 AMR

AF:

0.0205

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.0526

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.0406

ExAC

AF:

0.00641

AC:

139

Asia WGS

AF:

0.0240

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 11, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.85

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.91

PrimateAI

Pathogenic

0.83

Sift4G

Benign

0.29

T;.

Vest4

0.15

MPC

1.3

ClinPred

0.017

GERP RS

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over