chr20-23083972-G-C

Variant names:

• chr20-23083972-G-C
• rs146067424
• NM_012072.4:c.1937C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012072.4(CD93):​c.1937C>G​(p.Pro646Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000659 in 1,614,050 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P646L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00037 (2 hom.)
• Consequence: CD93 NM_012072.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007830083).
• BS2: High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012072.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD93	NM_012072.4	MANE Select	c.1937C>G	p.Pro646Arg	missense splice_region	Exon 2 of 2	NP_036204.2	Q9NPY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD93	ENST00000246006.5	TSL:1 MANE Select	c.1937C>G	p.Pro646Arg	missense splice_region	Exon 2 of 2	ENSP00000246006.4	Q9NPY3
	CD93	ENST00000850633.1		n.1937C>G		splice_region non_coding_transcript_exon	Exon 2 of 5	ENSP00000520912.1	Q9NPY3
	CD93	ENST00000850634.1		n.1937C>G		splice_region non_coding_transcript_exon	Exon 2 of 3	ENSP00000520913.1	Q9NPY3

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 515 AN: 152144 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000939 AC: 234 AN: 249152 AF XY: 0.000689

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000897

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000375 AC: 548 AN: 1461788 Hom.: 2 Cov.: 30 AF XY: 0.000311 AC XY: 226 AN XY: 727196

African (AFR) AF: 0.0128 AC: 430 AN: 33474

American (AMR) AF: 0.000760 AC: 34 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000872 AC: 5 AN: 5736

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111972

Other (OTH) AF: 0.00103 AC: 62 AN: 60378

GnomAD4 genome AF: 0.00338 AC: 515 AN: 152262 Hom.: 3 Cov.: 33 AF XY: 0.00317 AC XY: 236 AN XY: 74452

African (AFR) AF: 0.0115 AC: 477 AN: 41554

American (AMR) AF: 0.00203 AC: 31 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.00380

ESP6500AA AF: 0.0104 AC: 46

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00102 AC: 124

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.0060
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.15	T
Polyphen		0.58	P
Vest4		0.41
MVP		0.91
MPC		0.32
ClinPred		0.077	T
GERP RS		3.1
Varity_R		0.13
gMVP		0.22
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs146067424; hg19: chr20-23064609; COSMIC: COSV99079365;