Variant chr19-16893238-T-C 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.5528A>G(p.Gln1843Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,578,602 control chromosomes in the GnomAD database, including 84,483 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.27 ( 6377 hom., cov: 33)

Exomes 𝑓: 0.33 ( 78106 hom. )

Consequence

CPAMD8
NM_015692.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.50

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=8.649528E-4).

BP6

Variant 19-16893238-T-C is Benign according to our data. Variant chr19-16893238-T-C is described in ClinVar as [Benign]. Clinvar id is 1237649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 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.5528A>G	p.Gln1843Arg	missense_variant	42/42	ENST00000443236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPAMD8	ENST00000443236.7 linkuse as main transcript	c.5528A>G	p.Gln1843Arg	missense_variant	42/42	1	NM_015692.5	P2	Q8IZJ3-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41274

AN:

152132

Hom.:

6368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.297

AC:

56834

AN:

191656

Hom.:

8832

AF XY:

0.303

AC XY:

31488

AN XY:

103922

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.278

Gnomad ASJ exome

AF:

0.285

Gnomad EAS exome

AF:

0.134

Gnomad SAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.327

AC:

465708

AN:

1426352

Hom.:

78106

Cov.:

AF XY:

0.325

AC XY:

229943

AN XY:

706492

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.274

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.284

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.306

GnomAD4 genome

AF:

0.271

AC:

41321

AN:

152250

Hom.:

6377

Cov.:

AF XY:

0.272

AC XY:

20278

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.293

Gnomad4 ASJ

AF:

0.291

Gnomad4 EAS

AF:

0.137

Gnomad4 SAS

AF:

0.269

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.327

Hom.:

4356

Bravo

AF:

0.261

TwinsUK

AF:

0.349

AC:

1295

ALSPAC

AF:

0.336

AC:

1296

ESP6500AA

AF:

0.133

AC:

493

ESP6500EA

AF:

0.330

AC:

2683

ExAC

AF:

0.261

AC:

30840

Asia WGS

AF:

0.202

AC:

704

AN:

3478

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	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0090

DANN

Benign

0.23

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.16

MetaRNN

Benign

0.00086

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

Sift4G

Benign

0.51

Vest4

0.016

MPC

0.063

ClinPred

0.0021

GERP RS

-1.7

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