Genetic Variant CD93:p.Ser520Leu (chr20-23084634-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012072.4(CD93):c.1559C>T(p.Ser520Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00079 in 1,603,416 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00072 ( 4 hom., cov: 34)

Exomes 𝑓: 0.00080 ( 18 hom. )

Consequence

CD93
NM_012072.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.216

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004088968).

BP6

Variant 20-23084634-G-A is Benign according to our data. Variant chr20-23084634-G-A is described in ClinVar as [Benign]. Clinvar id is 770299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000798 (1158/1451078) while in subpopulation AMR AF= 0.0214 (937/43708). AF 95% confidence interval is 0.0203. There are 18 homozygotes in gnomad4_exome. There are 519 alleles in male gnomad4_exome subpopulation. Median coverage is 58. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4 link	c.1559C>T	p.Ser520Leu	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.1559C>T	p.Ser520Leu	missense_variant	Exon 1 of 2	1	NM_012072.4	ENSP00000246006.4		Q9NPY3

Frequencies

GnomAD3 genomes

AF:

0.000696

AC:

106

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00375

AC:

905

AN:

241626

Hom.:

AF XY:

0.00293

AC XY:

382

AN XY:

130538

show subpopulations

Gnomad AFR exome

AF:

0.000625

Gnomad AMR exome

AF:

0.0253

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.000275

Gnomad SAS exome

AF:

0.000520

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000119

Gnomad OTH exome

AF:

0.00189

GnomAD4 exome

AF:

0.000798

AC:

1158

AN:

1451078

Hom.:

Cov.:

AF XY:

0.000720

AC XY:

519

AN XY:

720992

show subpopulations

Gnomad4 AFR exome

AF:

0.000272

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.000505

Gnomad4 SAS exome

AF:

0.000672

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000669

Gnomad4 OTH exome

AF:

0.000986

GnomAD4 genome

AF:

0.000716

AC:

109

AN:

152338

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000243

Hom.:

Bravo

AF:

0.00184

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00259

AC:

314

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.3

DANN

Benign

0.88

DEOGEN2

Benign

0.075

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.0

REVEL

Benign

0.20

Sift

Benign

0.11

Sift4G

Uncertain

0.036

Polyphen

0.047

Vest4

0.063

MVP

0.74

MPC

0.066

ClinPred

0.0052

GERP RS

1.5

Varity_R

0.035

gMVP

0.33

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