Genetic Variant CD5L:p.Val305Ile (chr1-157833318-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005894.3(CD5L):c.913G>A(p.Val305Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000297 in 1,614,176 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

CD5L
NM_005894.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.27

Variant links:

Genes affected

CD5L (HGNC:1690): (CD5 molecule like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Predicted to act upstream of or within positive regulation of complement-dependent cytotoxicity and regulation of complement activation. Located in cell surface. [provided by Alliance of Genome Resources, Apr 2022]

CD5L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01652658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD5L	NM_005894.3 link	c.913G>A	p.Val305Ile	missense_variant	Exon 5 of 6	ENST00000368174.5	NP_005885.1	O43866
CD5L	NM_001347698.2 link	c.913G>A	p.Val305Ile	missense_variant	Exon 5 of 6		NP_001334627.1	O43866
CD5L	XM_017002806.2 link	c.913G>A	p.Val305Ile	missense_variant	Exon 5 of 6		XP_016858295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD5L	ENST00000368174.5 link	c.913G>A	p.Val305Ile	missense_variant	Exon 5 of 6	1	NM_005894.3	ENSP00000357156.4		O43866

Frequencies

GnomAD3 genomes

AF:

0.000467

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000449

AC:

113

AN:

251482

Hom.:

AF XY:

0.000405

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000343

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000279

AC:

408

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

211

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000466

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000270

Hom.:

Bravo

AF:

0.000608

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.913G>A (p.V305I) alteration is located in exon 5 (coding exon 5) of the CD5L gene. This alteration results from a G to A substitution at nucleotide position 913, causing the valine (V) at amino acid position 305 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.6

DANN

Uncertain

0.98

DEOGEN2

Benign

0.068

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.62

M_CAP

Benign

0.010

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.62

REVEL

Benign

0.085

Sift

Benign

0.31

Sift4G

Benign

0.25

Polyphen

0.55

Vest4

0.12

MVP

0.38

MPC

0.37

ClinPred

0.014

GERP RS

0.81

Varity_R

0.027

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over