chr19-16896339-G-A

Variant summary

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

The NM_015692.5(CPAMD8):​c.5276-13C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,595,808 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 13 hom., cov: 31)
Exomes 𝑓: 0.00054 ( 9 hom. )

Consequence

CPAMD8
NM_015692.5 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.649
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 19-16896339-G-A is Benign according to our data. Variant chr19-16896339-G-A is described in ClinVar as [Benign]. Clinvar id is 3020555.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00547 (833/152232) while in subpopulation AFR AF= 0.0193 (801/41550). AF 95% confidence interval is 0.0182. There are 13 homozygotes in gnomad4. There are 364 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CPAMD8NM_015692.5 linkuse as main transcriptc.5276-13C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000443236.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPAMD8ENST00000443236.7 linkuse as main transcriptc.5276-13C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_015692.5 P2Q8IZJ3-1

Frequencies

GnomAD3 genomes
AF:
0.00546
AC:
830
AN:
152116
Hom.:
13
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.00113
AC:
242
AN:
214824
Hom.:
3
AF XY:
0.000780
AC XY:
92
AN XY:
117892
show subpopulations
Gnomad AFR exome
AF:
0.0189
Gnomad AMR exome
AF:
0.000323
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000212
Gnomad OTH exome
AF:
0.000371
GnomAD4 exome
AF:
0.000539
AC:
778
AN:
1443576
Hom.:
9
Cov.:
32
AF XY:
0.000444
AC XY:
318
AN XY:
716530
show subpopulations
Gnomad4 AFR exome
AF:
0.0212
Gnomad4 AMR exome
AF:
0.000428
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000118
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000816
Gnomad4 OTH exome
AF:
0.000806
GnomAD4 genome
AF:
0.00547
AC:
833
AN:
152232
Hom.:
13
Cov.:
31
AF XY:
0.00489
AC XY:
364
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0193
Gnomad4 AMR
AF:
0.00144
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.0000858
Hom.:
0
Bravo
AF:
0.00615
Asia WGS
AF:
0.000867
AC:
3
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 13, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
6.0
DANN
Benign
0.90

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.

Other links and lift over

dbSNP: rs188097675; hg19: chr19-17007150; API