chr19-16893238-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015692.5(CPAMD8):ā€‹c.5528A>Gā€‹(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 (ā˜…ā˜…). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.27 ( 6377 hom., cov: 33)
Exomes š‘“: 0.33 ( 78106 hom. )

Consequence

CPAMD8
NM_015692.5 missense

Scores

13

Clinical Significance

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

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]

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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
CPAMD8NM_015692.5 linkuse as main transcriptc.5528A>G p.Gln1843Arg missense_variant 42/42 ENST00000443236.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CPAMD8ENST00000443236.7 linkuse as main transcriptc.5528A>G p.Gln1843Arg missense_variant 42/421 NM_015692.5 P2Q8IZJ3-1

Frequencies

GnomAD3 genomes
AF:
0.271
AC:
41274
AN:
152132
Hom.:
6368
Cov.:
33
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.:
32
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.:
33
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.82
T
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
N
LIST_S2
Benign
0.16
T
MetaRNN
Benign
0.00086
T
MetaSVM
Benign
-0.94
T
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.28
T
Sift4G
Benign
0.51
T
Vest4
0.016
MPC
0.063
ClinPred
0.0021
T
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.

Other links and lift over

dbSNP: rs1054533; hg19: chr19-17004049; COSMIC: COSV50185573; COSMIC: COSV50185573; API