rs6512158

Positions:

• chr19-17010723-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.486+741T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,022 control chromosomes in the GnomAD database, including 4,335 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 0.21 (4335 hom., cov: 31)
• Consequence: CPAMD8 NM_015692.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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]

ENSG00000268985 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPAMD8	NM_015692.5	c.486+741T>G		intron_variant		ENST00000443236.7	NP_056507.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPAMD8	ENST00000443236.7	c.486+741T>G		intron_variant		1	NM_015692.5	ENSP00000402505.3
CPAMD8	ENST00000291440.4	n.486+741T>G		intron_variant		1		ENSP00000291440.4
CPAMD8	ENST00000651564.2	c.486+741T>G		intron_variant				ENSP00000498697.2
ENSG00000268985	ENST00000595134.1	n.315+1220A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31928 AN: 151904 Hom.: 4314 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.210 AC: 31987 AN: 152022 Hom.: 4335 Cov.: 31 AF XY: 0.208 AC XY: 15493 AN XY: 74310

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0957

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.178

Alfa AF: 0.151 Hom.: 2499

Bravo AF: 0.215

Asia WGS AF: 0.128 AC: 445 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	0.82
DANN	Benign	0.55

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: rs6512158; hg19: chr19-17121533;