rs773857

Variant names:

• chr19-16908042-C-T
• rs773857
• NM_015692.5:c.3862-925G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015692.5(CPAMD8):​c.3862-925G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,022 control chromosomes in the GnomAD database, including 24,577 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 0.56 (24577 hom., cov: 32)
• Consequence: CPAMD8 NM_015692.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 3 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: ClinGen, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAMD8	NM_015692.5	c.3862-925G>A		intron_variant	Intron 29 of 41	ENST00000443236.7	NP_056507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPAMD8	ENST00000443236.7	c.3862-925G>A		intron_variant	Intron 29 of 41	1	NM_015692.5	ENSP00000402505.3
CPAMD8	ENST00000651564.2	c.3862-925G>A		intron_variant	Intron 29 of 41			ENSP00000498697.2
CPAMD8	ENST00000682780.1	c.37-925G>A		intron_variant	Intron 1 of 5			ENSP00000508109.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85680 AN: 151906 Hom.: 24576 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.552

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.564 AC: 85704 AN: 152022 Hom.: 24577 Cov.: 32 AF XY: 0.562 AC XY: 41774 AN XY: 74314

African (AFR) AF: 0.487 AC: 20215 AN: 41478

American (AMR) AF: 0.502 AC: 7667 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1827 AN: 3460

East Asian (EAS) AF: 0.411 AC: 2112 AN: 5144

South Asian (SAS) AF: 0.624 AC: 3008 AN: 4822

European-Finnish (FIN) AF: 0.647 AC: 6849 AN: 10580

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42136 AN: 67954

Other (OTH) AF: 0.551 AC: 1163 AN: 2112

Alfa AF: 0.589 Hom.: 3290

Bravo AF: 0.550

Asia WGS AF: 0.520 AC: 1811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs773857; hg19: chr19-17018852;