rs11666377

Variant names:

• chr19-17007623-C-T
• rs11666377
• NM_015692.5:c.559+882G>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.559+882G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,030 control chromosomes in the GnomAD database, including 2,787 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 0.18 (2787 hom., cov: 31)
• Consequence: CPAMD8 NM_015692.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 19 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 (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPAMD8	NM_015692.5	c.559+882G>A		intron_variant	Intron 7 of 41	ENST00000443236.7	NP_056507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPAMD8	ENST00000443236.7	c.559+882G>A		intron_variant	Intron 7 of 41	1	NM_015692.5	ENSP00000402505.3
CPAMD8	ENST00000291440.4	n.559+882G>A		intron_variant	Intron 7 of 14	1		ENSP00000291440.4
CPAMD8	ENST00000651564.2	c.559+882G>A		intron_variant	Intron 7 of 41			ENSP00000498697.2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27278 AN: 151912 Hom.: 2775 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.180 AC: 27315 AN: 152030 Hom.: 2787 Cov.: 31 AF XY: 0.179 AC XY: 13286 AN XY: 74314

African (AFR) AF: 0.276 AC: 11454 AN: 41472

American (AMR) AF: 0.118 AC: 1796 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.111 AC: 572 AN: 5152

South Asian (SAS) AF: 0.100 AC: 483 AN: 4816

European-Finnish (FIN) AF: 0.199 AC: 2103 AN: 10576

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10073 AN: 67972

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.154 Hom.: 5868

Bravo AF: 0.180

Asia WGS AF: 0.113 AC: 392 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	3.1
DANN	Benign	0.37
PhyloP100		0.72
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: rs11666377; hg19: chr19-17118433;