19-16919858-A-C

Position:

• chr19-16919858-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
CPAMD8	NM_015692.5	c.3629+2047T>G		intron_variant		ENST00000443236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPAMD8	ENST00000443236.7	c.3629+2047T>G		intron_variant		1	NM_015692.5	P2
CPAMD8	ENST00000651564.2	c.3629+2047T>G		intron_variant				A2

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

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.673

Alfa AF: 0.692 Hom.: 51877

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

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: rs773921; hg19: chr19-17030668;