7-28995812-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_031311.5(CPVL):c.1391G>A(p.Arg464Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,606,928 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (20 hom.)
• Consequence: CPVL NM_031311.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.33

Genes affected

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

CPVL-AS2 (HGNC:56138): (CPVL antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019909263).
• BP6: Variant 7-28995812-C-T is Benign according to our data. Variant chr7-28995812-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 733777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPVL	NM_031311.5	c.1391G>A	p.Arg464Gln	missense_variant	13/13	ENST00000265394.10
CPVL-AS2	NR_038965.1	n.133-353C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPVL	ENST00000265394.10	c.1391G>A	p.Arg464Gln	missense_variant	13/13	1	NM_031311.5	P1
CPVL-AS2	ENST00000609389.5	n.133-353C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 152058 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000966

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00237

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00459

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00288 AC: 706 AN: 245150 Hom.: 3 AF XY: 0.00301 AC XY: 399 AN XY: 132560

Gnomad AFR exome AF: 0.000626

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00232

Gnomad NFE exome AF: 0.00498

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.00430 AC: 6251 AN: 1454752 Hom.: 20 Cov.: 28 AF XY: 0.00430 AC XY: 3110 AN XY: 723646

Gnomad4 AFR exome AF: 0.000665

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.00131

Gnomad4 FIN exome AF: 0.00214

Gnomad4 NFE exome AF: 0.00523

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00269 AC: 409 AN: 152176 Hom.: 1 Cov.: 32 AF XY: 0.00237 AC XY: 176 AN XY: 74392

Gnomad4 AFR AF: 0.000963

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00237

Gnomad4 NFE AF: 0.00459

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00407 Hom.: 6

Bravo AF: 0.00245

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00465 AC: 40

ExAC AF: 0.00309 AC: 375

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00371

EpiControl AF: 0.00422

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Pathogenic	0.35
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Uncertain	0.45	T;T;.;T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.020	T;T;T;T
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	3.1	M;M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.42
MVP		0.98
MPC		0.37
ClinPred		0.059	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.83
gMVP		0.65

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: rs147771477; hg19: chr7-29035428; COSMIC: COSV55304151;