Variant chr19-16895976-G-A 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+200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 704,508 control chromosomes in the GnomAD database, including 32,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5982 hom., cov: 28)

Exomes 𝑓: 0.30 ( 26821 hom. )

Consequence

CPAMD8
NM_015692.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0160

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 19-16895976-G-A is Benign according to our data. Variant chr19-16895976-G-A is described in ClinVar as [Benign]. Clinvar id is 1278790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 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+200C>T		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+200C>T		intron_variant		1	NM_015692.5	P2	Q8IZJ3-1

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39187

AN:

151126

Hom.:

5979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.0606

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.279

AC:

37562

AN:

134512

Hom.:

5751

AF XY:

0.285

AC XY:

21093

AN XY:

74052

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.0630

Gnomad SAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.353

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.300

AC:

165980

AN:

553264

Hom.:

26821

Cov.:

AF XY:

0.301

AC XY:

90112

AN XY:

299592

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.272

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.0681

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.289

GnomAD4 genome

AF:

0.259

AC:

39216

AN:

151244

Hom.:

5982

Cov.:

AF XY:

0.259

AC XY:

19132

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.113

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.290

Gnomad4 EAS

AF:

0.0609

Gnomad4 SAS

AF:

0.257

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.338

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.296

Hom.:

1476

Bravo

AF:

0.251

Asia WGS

AF:

0.166

AC:

578

AN:

3478

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 10, 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

1.8

DANN

Benign

0.92

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