Genetic Variant CD93:p.Val543Ile (chr20-23084566-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_012072.4(CD93):c.1627G>A(p.Val543Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00021 in 1,612,406 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00077 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CD93
NM_012072.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.57

Variant links:

Genes affected

CD93 (HGNC:15855): (CD93 molecule) The protein encoded by this gene is a cell-surface glycoprotein and type I membrane protein that was originally identified as a myeloid cell-specific marker. The encoded protein was once thought to be a receptor for C1q, but now is thought to instead be involved in intercellular adhesion and in the clearance of apoptotic cells. The intracellular cytoplasmic tail of this protein has been found to interact with moesin, a protein known to play a role in linking transmembrane proteins to the cytoskeleton and in the remodelling of the cytoskeleton. [provided by RefSeq, Jul 2008]

CD93 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0063326657).

BP6

Variant 20-23084566-C-T is Benign according to our data. Variant chr20-23084566-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3051666.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4 link	c.1627G>A	p.Val543Ile	missense_variant	Exon 1 of 2	ENST00000246006.5	NP_036204.2	Q9NPY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD93	ENST00000246006.5 link	c.1627G>A	p.Val543Ile	missense_variant	Exon 1 of 2	1	NM_012072.4	ENSP00000246006.4		Q9NPY3

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

117

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000419

AC:

105

AN:

250482

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.00305

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000152

AC:

222

AN:

1460074

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

726296

show subpopulations

Gnomad4 AFR exome

AF:

0.00335

Gnomad4 AMR exome

AF:

0.000964

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152332

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00267

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000190

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000395

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CD93-related disorder

Benign:1

Feb 28, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.0070

DANN

Benign

0.61

DEOGEN2

Benign

0.071

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.86

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.12

REVEL

Benign

0.21

Sift

Benign

0.30

Sift4G

Uncertain

0.060

Polyphen

0.0040

Vest4

0.012

MVP

0.45

MPC

0.061

ClinPred

0.015

GERP RS

-8.6

Varity_R

0.025

gMVP

0.16

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

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