rs11666377

Positions:

• chr19-17007623-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CPAMD8	NM_015692.5	c.559+882G>A		intron_variant		ENST00000443236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPAMD8	ENST00000443236.7	c.559+882G>A		intron_variant		1	NM_015692.5	P2
CPAMD8	ENST00000291440.4	c.559+882G>A		intron_variant, NMD_transcript_variant		1
CPAMD8	ENST00000651564.2	c.559+882G>A		intron_variant				A2

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

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.164

Alfa AF: 0.150 Hom.: 3710

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11666377; hg19: chr19-17118433;