Genetic Variant CD93:p.Thr493Ile (chr20-23084715-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_012072.4(CD93):c.1478C>T(p.Thr493Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,596,720 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 34)

Exomes 𝑓: 0.00070 ( 6 hom. )

Consequence

CD93
NM_012072.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00600

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00368917).

BP6

Variant 20-23084715-G-A is Benign according to our data. Variant chr20-23084715-G-A is described in ClinVar as Benign. ClinVar VariationId is 734870.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012072.4. 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
	CD93	NM_012072.4	MANE Select	c.1478C>T	p.Thr493Ile	missense	Exon 1 of 2	NP_036204.2	Q9NPY3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD93	ENST00000246006.5	TSL:1 MANE Select	c.1478C>T	p.Thr493Ile	missense	Exon 1 of 2	ENSP00000246006.4	Q9NPY3
CD93	ENST00000850633.1		n.1478C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000520912.1	Q9NPY3
CD93	ENST00000850634.1		n.1478C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000520913.1	Q9NPY3

Frequencies

GnomAD3 genomes

AF:

0.00452

AC:

688

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

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:

0.000279

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00155

AC:

364

AN:

234932

AF XY:

0.00127

show subpopulations

Gnomad AFR exome

AF:

0.0157

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000460

Gnomad OTH exome

AF:

0.00143

GnomAD4 exome

AF:

0.000703

AC:

1016

AN:

1444436

Hom.:

Cov.:

AF XY:

0.000695

AC XY:

499

AN XY:

717606

show subpopulations

African (AFR)

AF:

0.0154

AC:

505

AN:

32750

American (AMR)

AF:

0.00179

AC:

AN:

42348

Ashkenazi Jewish (ASJ)

AF:

0.0000813

AC:

AN:

24588

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.0000716

AC:

AN:

83756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52138

Middle Eastern (MID)

AF:

0.00302

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.000289

AC:

319

AN:

1104134

Other (OTH)

AF:

0.00153

AC:

AN:

59504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00454

AC:

691

AN:

152284

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

335

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0152

AC:

632

AN:

41570

American (AMR)

AF:

0.00183

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68014

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

104

138

173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.00493

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0168

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00181

AC:

220

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.1

(source)

DANN

Benign

0.53

DEOGEN2

Benign

0.13

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.3

PhyloP100

-0.0060

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.58

REVEL

Benign

0.11

Sift

Benign

0.47

Sift4G

Benign

0.46

Polyphen

0.011

Vest4

0.097

MVP

0.83

MPC

0.079

ClinPred

0.00064

GERP RS

-2.6

Varity_R

0.028

gMVP

0.47

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over