19-16892978-T-G

Variant names:

• chr19-16892978-T-G
• rs773901
• NM_015692.5:c.*130A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015692.5(CPAMD8):​c.*130A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 766,154 control chromosomes in the GnomAD database, including 115,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (27645 hom., cov: 32)
  • Exomes 𝑓: 0.53 (87986 hom.)
• Consequence: CPAMD8 NM_015692.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.58
• Publications: 26 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: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 19-16892978-T-G is Benign according to our data. Variant chr19-16892978-T-G is described in ClinVar as Benign. ClinVar VariationId is 1240872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015692.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAMD8	NM_015692.5	MANE Select	c.*130A>C		3_prime_UTR	Exon 42 of 42	NP_056507.3	Q8IZJ3-1
	CPAMD8	NR_147452.2		n.1698A>C		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPAMD8	ENST00000443236.7	TSL:1 MANE Select	c.*130A>C		3_prime_UTR	Exon 42 of 42	ENSP00000402505.3	Q8IZJ3-1
	CPAMD8	ENST00000942844.1		c.*130A>C		3_prime_UTR	Exon 42 of 42	ENSP00000612903.1
	CPAMD8	ENST00000651564.2		c.*1438A>C		3_prime_UTR	Exon 42 of 42	ENSP00000498697.2	Q8IZJ3-2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90132 AN: 151940 Hom.: 27591 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.608

GnomAD2 exomes AF: 0.533 AC: 127013 AN: 238208 AF XY: 0.535

Gnomad AFR exome AF: 0.759

Gnomad AMR exome AF: 0.524

Gnomad ASJ exome AF: 0.567

Gnomad EAS exome AF: 0.324

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.529

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.529 AC: 325088 AN: 614096 Hom.: 87986 Cov.: 3 AF XY: 0.532 AC XY: 178020 AN XY: 334760

African (AFR) AF: 0.752 AC: 13242 AN: 17600

American (AMR) AF: 0.527 AC: 22890 AN: 43454

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 11738 AN: 20856

East Asian (EAS) AF: 0.311 AC: 11187 AN: 35924

South Asian (SAS) AF: 0.554 AC: 38032 AN: 68688

European-Finnish (FIN) AF: 0.538 AC: 23755 AN: 44158

Middle Eastern (MID) AF: 0.624 AC: 2579 AN: 4132

European-Non Finnish (NFE) AF: 0.531 AC: 183838 AN: 346510

Other (OTH) AF: 0.544 AC: 17827 AN: 32774

GnomAD4 genome AF: 0.594 AC: 90258 AN: 152058 Hom.: 27645 Cov.: 32 AF XY: 0.593 AC XY: 44088 AN XY: 74326

African (AFR) AF: 0.751 AC: 31157 AN: 41464

American (AMR) AF: 0.576 AC: 8811 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1979 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1662 AN: 5170

South Asian (SAS) AF: 0.541 AC: 2611 AN: 4824

European-Finnish (FIN) AF: 0.563 AC: 5961 AN: 10580

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36075 AN: 67950

Other (OTH) AF: 0.608 AC: 1285 AN: 2112

Alfa AF: 0.547 Hom.: 90176

Bravo AF: 0.601

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.043
DANN	Benign	0.49
PhyloP100		-1.6
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: rs773901; hg19: chr19-17003789; COSMIC: COSV50185984; COSMIC: COSV50185984;