rs2353203

Variant names:

• chr19-16989170-G-A
• rs2353203
• NM_015692.5:c.1395+473C>T

Variant summary

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

The NM_015692.5(CPAMD8):​c.1395+473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,974 control chromosomes in the GnomAD database, including 22,155 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 0.53 (22155 hom., cov: 31)
• Consequence: CPAMD8 NM_015692.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAMD8	NM_015692.5	c.1395+473C>T		intron_variant	Intron 13 of 41	ENST00000443236.7	NP_056507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPAMD8	ENST00000443236.7	c.1395+473C>T		intron_variant	Intron 13 of 41	1	NM_015692.5	ENSP00000402505.3
CPAMD8	ENST00000291440.4	n.1266+4246C>T		intron_variant	Intron 12 of 14	1		ENSP00000291440.4
CPAMD8	ENST00000651564.2	c.1395+473C>T		intron_variant	Intron 13 of 41			ENSP00000498697.2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80184 AN: 151854 Hom.: 22143 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.528 AC: 80236 AN: 151974 Hom.: 22155 Cov.: 31 AF XY: 0.526 AC XY: 39104 AN XY: 74284

African (AFR) AF: 0.688 AC: 28501 AN: 41452

American (AMR) AF: 0.467 AC: 7128 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2072 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3104 AN: 5154

South Asian (SAS) AF: 0.409 AC: 1968 AN: 4810

European-Finnish (FIN) AF: 0.462 AC: 4880 AN: 10562

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30914 AN: 67950

Other (OTH) AF: 0.528 AC: 1114 AN: 2108

Alfa AF: 0.484 Hom.: 54902

Bravo AF: 0.541

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.87
DANN	Benign	0.83
PhyloP100		-0.57
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: rs2353203; hg19: chr19-17099980;