rs773921

Variant names:

• chr19-16919858-A-C
• rs773921
• NM_015692.5:c.3629+2047T>G

Variant summary

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

The NM_015692.5(CPAMD8):​c.3629+2047T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,116 control chromosomes in the GnomAD database, including 35,410 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 0.68 (35410 hom., cov: 33)
• Consequence: CPAMD8 NM_015692.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAMD8	NM_015692.5	c.3629+2047T>G		intron_variant	Intron 27 of 41	ENST00000443236.7	NP_056507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPAMD8	ENST00000443236.7	c.3629+2047T>G		intron_variant	Intron 27 of 41	1	NM_015692.5	ENSP00000402505.3
CPAMD8	ENST00000651564.2	c.3629+2047T>G		intron_variant	Intron 27 of 41			ENSP00000498697.2

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103386 AN: 151998 Hom.: 35350 Cov.: 33

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.680 AC: 103506 AN: 152116 Hom.: 35410 Cov.: 33 AF XY: 0.682 AC XY: 50716 AN XY: 74366

African (AFR) AF: 0.636 AC: 26395 AN: 41484

American (AMR) AF: 0.675 AC: 10310 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2430 AN: 3470

East Asian (EAS) AF: 0.751 AC: 3884 AN: 5170

South Asian (SAS) AF: 0.688 AC: 3315 AN: 4818

European-Finnish (FIN) AF: 0.694 AC: 7349 AN: 10592

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.701 AC: 47681 AN: 67990

Other (OTH) AF: 0.673 AC: 1418 AN: 2106

Alfa AF: 0.691 Hom.: 72072

Bravo AF: 0.674

Asia WGS AF: 0.727 AC: 2526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.52
PhyloP100		-1.3
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: rs773921; hg19: chr19-17030668;