19-16897042-G-C

Variant names:

• chr19-16897042-G-C
• rs2227383
• NM_015692.5:c.5066-377C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015692.5(CPAMD8):​c.5066-377C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 9,976 control chromosomes in the GnomAD database, including 216 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (3062 hom., cov: 9)
  • Exomes 𝑓: 0.14 (216 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPAMD8 NM_015692.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAMD8	NM_015692.5	c.5066-377C>G		intron_variant	Intron 39 of 41	ENST00000443236.7	NP_056507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPAMD8	ENST00000443236.7	c.5066-377C>G		intron_variant	Intron 39 of 41	1	NM_015692.5	ENSP00000402505.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 21135 AN: 58984 Hom.: 3061 Cov.: 9 FAILED QC

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.141 AC: 1409 AN: 9976 Hom.: 216 AF XY: 0.146 AC XY: 727 AN XY: 4968

Gnomad4 AFR exome AF: 0.0423

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0160

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.358 AC: 21153 AN: 59020 Hom.: 3062 Cov.: 9 AF XY: 0.354 AC XY: 9637 AN XY: 27192

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.358

Alfa AF: 0.157 Hom.: 397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.1
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs2227383; hg19: chr19-17007853;