Genetic Variant CD93:p.Arg496Arg (chr20-23084705-A-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_012072.4(CD93):c.1488T>C(p.Arg496Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,588,624 control chromosomes in the GnomAD database, including 451,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.76 ( 44107 hom., cov: 34)

Exomes 𝑓: 0.75 ( 407166 hom. )

Consequence

CD93
NM_012072.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.316

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 20-23084705-A-G is Benign according to our data. Variant chr20-23084705-A-G is described in ClinVar as [Benign]. Clinvar id is 2688438.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.316 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4 link	c.1488T>C	p.Arg496Arg	synonymous_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.1488T>C	p.Arg496Arg	synonymous_variant	Exon 1 of 2	1	NM_012072.4	ENSP00000246006.4		Q9NPY3

Frequencies

GnomAD3 genomes

AF:

0.760

AC:

115514

AN:

151932

Hom.:

44051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.758

Gnomad AMI

AF:

0.959

Gnomad AMR

AF:

0.798

Gnomad ASJ

AF:

0.800

Gnomad EAS

AF:

0.815

Gnomad SAS

AF:

0.785

Gnomad FIN

AF:

0.691

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.752

Gnomad OTH

AF:

0.787

GnomAD3 exomes

AF:

0.773

AC:

177903

AN:

230284

Hom.:

69044

AF XY:

0.769

AC XY:

95721

AN XY:

124400

show subpopulations

Gnomad AFR exome

AF:

0.760

Gnomad AMR exome

AF:

0.850

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.828

Gnomad SAS exome

AF:

0.776

Gnomad FIN exome

AF:

0.693

Gnomad NFE exome

AF:

0.753

Gnomad OTH exome

AF:

0.781

GnomAD4 exome

AF:

0.752

AC:

1080765

AN:

1436574

Hom.:

407166

Cov.:

AF XY:

0.753

AC XY:

536560

AN XY:

712676

show subpopulations

Gnomad4 AFR exome

AF:

0.763

Gnomad4 AMR exome

AF:

0.841

Gnomad4 ASJ exome

AF:

0.799

Gnomad4 EAS exome

AF:

0.824

Gnomad4 SAS exome

AF:

0.775

Gnomad4 FIN exome

AF:

0.693

Gnomad4 NFE exome

AF:

0.745

Gnomad4 OTH exome

AF:

0.762

GnomAD4 genome

AF:

0.760

AC:

115631

AN:

152050

Hom.:

44107

Cov.:

AF XY:

0.759

AC XY:

56379

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.758

Gnomad4 AMR

AF:

0.799

Gnomad4 ASJ

AF:

0.800

Gnomad4 EAS

AF:

0.816

Gnomad4 SAS

AF:

0.785

Gnomad4 FIN

AF:

0.691

Gnomad4 NFE

AF:

0.752

Gnomad4 OTH

AF:

0.789

Alfa

AF:

0.761

Hom.:

65274

Bravo

AF:

0.770

Asia WGS

AF:

0.798

AC:

2775

AN:

3478

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 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.73

DANN

Benign

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