19-16896136-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.152

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	c.5426+40T>G		intron_variant		ENST00000443236.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3602 AN: 149742 Hom.: 160 Cov.: 31

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.: 65 AF XY: 0.00495 AC XY: 669 AN XY: 135288

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.: 31 AF XY: 0.00238 AC XY: 1726 AN XY: 725294

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.: 31 AF XY: 0.0232 AC XY: 1700 AN XY: 73170

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.: 13

Bravo AF: 0.0284

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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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

Other links and lift over

dbSNP: rs2227368; hg19: chr19-17006947;