NM_012072.4:c.1488T>C

Variant names:

• chr20-23084705-A-G
• rs3746732
• NM_012072.4:c.1488T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.316
• Publications: 19 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 -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 VariationId 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.

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.1488T>C	p.Arg496Arg	synonymous	Exon 1 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.1488T>C	p.Arg496Arg	synonymous	Exon 1 of 2	ENSP00000246006.4	Q9NPY3
	CD93	ENST00000850633.1		n.1488T>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000520912.1	Q9NPY3
	CD93	ENST00000850634.1		n.1488T>C		non_coding_transcript_exon	Exon 1 of 3	ENSP00000520913.1	Q9NPY3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115514 AN: 151932 Hom.: 44051 Cov.: 34

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

GnomAD2 exomes AF: 0.773 AC: 177903 AN: 230284 AF XY: 0.769

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 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.: 63 AF XY: 0.753 AC XY: 536560 AN XY: 712676

African (AFR) AF: 0.763 AC: 24788 AN: 32478

American (AMR) AF: 0.841 AC: 34842 AN: 41416

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 19192 AN: 24018

East Asian (EAS) AF: 0.824 AC: 32562 AN: 39494

South Asian (SAS) AF: 0.775 AC: 63909 AN: 82458

European-Finnish (FIN) AF: 0.693 AC: 35941 AN: 51832

Middle Eastern (MID) AF: 0.808 AC: 4537 AN: 5616

European-Non Finnish (NFE) AF: 0.745 AC: 819893 AN: 1100104

Other (OTH) AF: 0.762 AC: 45101 AN: 59158

GnomAD4 genome AF: 0.760 AC: 115631 AN: 152050 Hom.: 44107 Cov.: 34 AF XY: 0.759 AC XY: 56379 AN XY: 74304

African (AFR) AF: 0.758 AC: 31453 AN: 41468

American (AMR) AF: 0.799 AC: 12221 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2776 AN: 3470

East Asian (EAS) AF: 0.816 AC: 4181 AN: 5126

South Asian (SAS) AF: 0.785 AC: 3792 AN: 4830

European-Finnish (FIN) AF: 0.691 AC: 7318 AN: 10586

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51115 AN: 67950

Other (OTH) AF: 0.789 AC: 1668 AN: 2114

Alfa AF: 0.762 Hom.: 80216

Bravo AF: 0.770

Asia WGS AF: 0.798 AC: 2775 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.33
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3746732; hg19: chr20-23065342; COSMIC: COSV55667574;