19-16897042-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015692.5(CPAMD8):​c.5066-377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 9)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CPAMD8 NM_015692.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.53
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• anterior segment dysgenesis 8

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015692.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAMD8	NM_015692.5	MANE Select	c.5066-377C>T		intron	N/A	NP_056507.3	Q8IZJ3-1
	CPAMD8	NR_147452.2		n.-95C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAMD8	ENST00000443236.7	TSL:1 MANE Select	c.5066-377C>T		intron	N/A	ENSP00000402505.3	Q8IZJ3-1
	CPAMD8	ENST00000942844.1		c.5030-377C>T		intron	N/A	ENSP00000612903.1
	CPAMD8	ENST00000651564.2		c.5066-377C>T		intron	N/A	ENSP00000498697.2	Q8IZJ3-2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 59618 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 10008 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4990

African (AFR) AF: 0.00 AC: 0 AN: 570

American (AMR) AF: 0.00 AC: 0 AN: 264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 464

East Asian (EAS) AF: 0.00 AC: 0 AN: 874

South Asian (SAS) AF: 0.00 AC: 0 AN: 136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 62

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6452

Other (OTH) AF: 0.00 AC: 0 AN: 716

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 59618 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 27452

African (AFR) AF: 0.00 AC: 0 AN: 11840

American (AMR) AF: 0.00 AC: 0 AN: 5424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1732

East Asian (EAS) AF: 0.00 AC: 0 AN: 1324

South Asian (SAS) AF: 0.00 AC: 0 AN: 1512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 33264

Other (OTH) AF: 0.00 AC: 0 AN: 752

Alfa AF: 0.00 Hom.: 397

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.64
PhyloP100		-5.5

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

Other links and lift over

dbSNP: rs2227383; hg19: chr19-17007853;