Variant 19-16896136-A-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.5426+40T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 1,607,440 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 161 hom., cov: 31)

Exomes 𝑓: 0.0028 ( 170 hom. )

Consequence

CPAMD8
NM_015692.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.152

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 (BayesDel_noAF=-0.9).

BP6

Variant 19-16896136-A-C is Benign according to our data. Variant chr19-16896136-A-C is described in ClinVar as [Benign]. Clinvar id is 1278930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0819 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.5426+40T>G		intron_variant		ENST00000443236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPAMD8	ENST00000443236.7 linkuse as main transcript	c.5426+40T>G		intron_variant		1	NM_015692.5	P2	Q8IZJ3-1

Frequencies

GnomAD3 genomes

AF:

0.0241

AC:

3602

AN:

149742

Hom.:

160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0843

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00978

Gnomad ASJ

AF:

0.00608

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000178

Gnomad OTH

AF:

0.0151

GnomAD3 exomes

AF:

0.00657

AC:

1634

AN:

248838

Hom.:

AF XY:

0.00495

AC XY:

669

AN XY:

135288

show subpopulations

Gnomad AFR exome

AF:

0.0883

Gnomad AMR exome

AF:

0.00446

Gnomad ASJ exome

AF:

0.00777

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00275

AC:

4014

AN:

1457586

Hom.:

170

Cov.:

AF XY:

0.00238

AC XY:

1726

AN XY:

725294

show subpopulations

Gnomad4 AFR exome

AF:

0.0912

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.00973

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000100

Gnomad4 OTH exome

AF:

0.00594

GnomAD4 genome

AF:

0.0241

AC:

3610

AN:

149854

Hom.:

161

Cov.:

AF XY:

0.0232

AC XY:

1700

AN XY:

73170

show subpopulations

Gnomad4 AFR

AF:

0.0842

Gnomad4 AMR

AF:

0.00977

Gnomad4 ASJ

AF:

0.00608

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000178

Gnomad4 OTH

AF:

0.0149

Alfa

AF:

0.0161

Hom.:

Bravo

AF:

0.0284

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.3

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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