Genetic Variant CD93:c.1934+86G>A (chr20-23084173-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_012072.4(CD93):c.1934+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,519,054 control chromosomes in the GnomAD database, including 244,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.52 ( 21503 hom., cov: 32)

Exomes 𝑓: 0.57 ( 222544 hom. )

Consequence

CD93
NM_012072.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0590

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-23084173-C-T is Benign according to our data. Variant chr20-23084173-C-T is described in ClinVar as [Benign]. Clinvar id is 2688534.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD93	NM_012072.4 link	c.1934+86G>A		intron_variant	Intron 1 of 1	ENST00000246006.5	NP_036204.2	Q9NPY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD93	ENST00000246006.5 link	c.1934+86G>A		intron_variant	Intron 1 of 1	1	NM_012072.4	ENSP00000246006.4		Q9NPY3

Frequencies

GnomAD3 genomes

AF:

0.516

AC:

78359

AN:

151920

Hom.:

21487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.614

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.785

Gnomad SAS

AF:

0.678

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.677

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.582

GnomAD4 exome

AF:

0.565

AC:

773002

AN:

1367016

Hom.:

222544

Cov.:

AF XY:

0.569

AC XY:

386902

AN XY:

679714

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.657

Gnomad4 ASJ exome

AF:

0.670

Gnomad4 EAS exome

AF:

0.796

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.396

Gnomad4 NFE exome

AF:

0.557

Gnomad4 OTH exome

AF:

0.578

GnomAD4 genome

AF:

0.516

AC:

78416

AN:

152038

Hom.:

21503

Cov.:

AF XY:

0.513

AC XY:

38134

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.614

Gnomad4 ASJ

AF:

0.674

Gnomad4 EAS

AF:

0.786

Gnomad4 SAS

AF:

0.678

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.386

Hom.:

1038

Bravo

AF:

0.530

Asia WGS

AF:

0.704

AC:

2449

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 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

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.9

DANN

Benign

0.63

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