Variant 19-16896260-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015692.5(CPAMD8):c.5342C>G(p.Pro1781Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,613,532 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

CPAMD8
NM_015692.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.73

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032495558).

BP6

Variant 19-16896260-G-C is Benign according to our data. Variant chr19-16896260-G-C is described in ClinVar as [Benign]. Clinvar id is 2152472.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000348 (53/152234) while in subpopulation EAS AF= 0.0097 (50/5156). AF 95% confidence interval is 0.00756. There are 0 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPAMD8	NM_015692.5 linkuse as main transcript	c.5342C>G	p.Pro1781Arg	missense_variant	41/42	ENST00000443236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPAMD8	ENST00000443236.7 linkuse as main transcript	c.5342C>G	p.Pro1781Arg	missense_variant	41/42	1	NM_015692.5	P2	Q8IZJ3-1

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00986

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000705

AC:

175

AN:

248292

Hom.:

AF XY:

0.000666

AC XY:

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00958

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000175

AC:

255

AN:

1461298

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

129

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00584

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000348

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00970

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000552

ExAC

AF:

0.000505

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 18, 2022

- -

CPAMD8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.49

DANN

Benign

0.48

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.39

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

Sift4G

Uncertain

0.049

Vest4

0.17

MVP

0.072

MPC

0.063

ClinPred

0.015

GERP RS

-3.0

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