chr20-23084572-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_012072.4(CD93):c.1621C>T(p.Pro541Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,613,292 control chromosomes in the GnomAD database, including 250,691 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 0.51 ( 20646 hom., cov: 34)

Exomes 𝑓: 0.56 ( 230045 hom. )

Consequence

CD93
NM_012072.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

Publications

34 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.35512455E-5).

BP6

Variant 20-23084572-G-A is Benign according to our data. Variant chr20-23084572-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688535.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4 link	c.1621C>T	p.Pro541Ser	missense_variant	Exon 1 of 2	ENST00000246006.5	NP_036204.2	Q9NPY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD93	ENST00000246006.5 link	c.1621C>T	p.Pro541Ser	missense_variant	Exon 1 of 2	1	NM_012072.4	ENSP00000246006.4	Q9NPY3
CD93	ENST00000850633.1 link	n.1621C>T		non_coding_transcript_exon_variant	Exon 1 of 5			ENSP00000520912.1
CD93	ENST00000850634.1 link	n.1621C>T		non_coding_transcript_exon_variant	Exon 1 of 3			ENSP00000520913.1
CD93	ENST00000850635.1 link	n.1621C>T		non_coding_transcript_exon_variant	Exon 1 of 4			ENSP00000520914.1

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

77464

AN:

151982

Hom.:

20623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.643

Gnomad EAS

AF:

0.628

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.558

GnomAD2 exomes

AF:

0.566

AC:

141714

AN:

250180

AF XY:

0.572

show subpopulations

Gnomad AFR exome

AF:

0.372

Gnomad AMR exome

AF:

0.650

Gnomad ASJ exome

AF:

0.645

Gnomad EAS exome

AF:

0.641

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.604

GnomAD4 exome

AF:

0.558

AC:

815062

AN:

1461192

Hom.:

230045

Cov.:

AF XY:

0.562

AC XY:

408280

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.372

AC:

12436

AN:

33444

American (AMR)

AF:

0.646

AC:

28871

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

16836

AN:

26106

East Asian (EAS)

AF:

0.662

AC:

26264

AN:

39696

South Asian (SAS)

AF:

0.644

AC:

55506

AN:

86248

European-Finnish (FIN)

AF:

0.394

AC:

20886

AN:

53030

Middle Eastern (MID)

AF:

0.677

AC:

3905

AN:

5768

European-Non Finnish (NFE)

AF:

0.554

AC:

616351

AN:

1111820

Other (OTH)

AF:

0.563

AC:

34007

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

23622

47244

70865

94487

118109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17326

34652

51978

69304

86630

<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:

0.510

AC:

77532

AN:

152100

Hom.:

20646

Cov.:

AF XY:

0.504

AC XY:

37494

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.374

AC:

15507

AN:

41496

American (AMR)

AF:

0.593

AC:

9078

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

2233

AN:

3472

East Asian (EAS)

AF:

0.629

AC:

3239

AN:

5148

South Asian (SAS)

AF:

0.662

AC:

3196

AN:

4828

European-Finnish (FIN)

AF:

0.377

AC:

3988

AN:

10580

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38187

AN:

67958

Other (OTH)

AF:

0.562

AC:

1186

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1936

3872

5808

7744

9680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.564

Hom.:

53385

Bravo

AF:

0.523

TwinsUK

AF:

0.556

AC:

2063

ALSPAC

AF:

0.543

AC:

2091

ESP6500AA

AF:

0.367

AC:

1618

ESP6500EA

AF:

0.567

AC:

4873

ExAC

AF:

0.561

AC:

68172

Asia WGS

AF:

0.630

AC:

2192

AN:

3478

EpiCase

AF:

0.582

EpiControl

AF:

0.586

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 76. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.4

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.098

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.51

MetaRNN

Benign

0.000014

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.4

PhyloP100

1.6

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Benign

0.36

Sift4G

Benign

0.36

Polyphen

0.19

Vest4

0.028

MPC

0.13

ClinPred

0.012

GERP RS

3.8

Varity_R

0.035

gMVP

0.33

Mutation Taster

=97/3

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over