Genetic Variant CD93:p.Pro646Arg (chr20-23083972-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012072.4(CD93):c.1937C>G(p.Pro646Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000659 in 1,614,050 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 2 hom. )

Consequence

CD93
NM_012072.4 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007830083).

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4 link	c.1937C>G	p.Pro646Arg	missense_variant, splice_region_variant	Exon 2 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.1937C>G	p.Pro646Arg	missense_variant, splice_region_variant	Exon 2 of 2	1	NM_012072.4	ENSP00000246006.4		Q9NPY3

Frequencies

GnomAD3 genomes

AF:

0.00338

AC:

515

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

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:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000939

AC:

234

AN:

249152

Hom.:

AF XY:

0.000689

AC XY:

AN XY:

134888

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000375

AC:

548

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000311

AC XY:

226

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00338

AC:

515

AN:

152262

Hom.:

Cov.:

AF XY:

0.00317

AC XY:

236

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.00380

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00102

AC:

124

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.16

Eigen

Benign

-0.0060

Eigen_PC

Benign

0.021

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.0

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Benign

0.15

Polyphen

0.58

Vest4

0.41

MVP

0.91

MPC

0.32

ClinPred

0.077

GERP RS

3.1

Varity_R

0.13

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over