20-23084634-G-A

Position:

• chr20-23084634-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000246006.5(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 ENST00000246006.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.216

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]

ACMG classification

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/exons	MANE	Protein	UniProt
CD93	NM_012072.4	c.1559C>T	p.Ser520Leu	missense_variant	1/2	ENST00000246006.5	NP_036204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD93	ENST00000246006.5	c.1559C>T	p.Ser520Leu	missense_variant	1/2	1	NM_012072.4	ENSP00000246006	P1

Frequencies

GnomAD3 genomes AF: 0.000696 AC: 106 AN: 152220 Hom.: 4 Cov.: 34

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.: 15 AF XY: 0.00293 AC XY: 382 AN XY: 130538

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.: 18 Cov.: 58 AF XY: 0.000720 AC XY: 519 AN XY: 720992

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.: 4 Cov.: 34 AF XY: 0.000658 AC XY: 49 AN XY: 74484

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.: 0

Bravo AF: 0.00184

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00259 AC: 314

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.3
DANN	Benign	0.88
DEOGEN2	Benign	0.075	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.20
Sift	Benign	0.11	T
Sift4G	Uncertain	0.036	D
Polyphen		0.047	B
Vest4		0.063
MVP		0.74
MPC		0.066
ClinPred		0.0052	T
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

Other links and lift over

dbSNP: rs143062108; hg19: chr20-23065271; COSMIC: COSV55668029;