rs3746731

Variant names:

• chr20-23084572-G-A
• rs3746731
• NM_012072.4:c.1621C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-23084572-G-A
• chr20-23084572-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012072.4(CD93):​c.1621C>T​(p.Pro541Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,613,292 control chromosomes in the GnomAD database, including 250,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (20646 hom., cov: 34)
  • Exomes 𝑓: 0.56 (230045 hom.)
• Consequence: CD93 NM_012072.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.55
• Publications: 34 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.35512455E-5).
• BP6: Variant 20-23084572-G-A is Benign according to our data. Variant chr20-23084572-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 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.1621C>T	p.Pro541Ser	missense	Exon 1 of 2	NP_036204.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD93	ENST00000246006.5	TSL:1 MANE Select	c.1621C>T	p.Pro541Ser	missense	Exon 1 of 2	ENSP00000246006.4
	CD93	ENST00000850633.1		n.1621C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000520912.1
	CD93	ENST00000850634.1		n.1621C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000520913.1

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77464 AN: 151982 Hom.: 20623 Cov.: 34

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.558

GnomAD2 exomes AF: 0.566 AC: 141714 AN: 250180 AF XY: 0.572

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.650

Gnomad ASJ exome AF: 0.645

Gnomad EAS exome AF: 0.641

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.561

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.558 AC: 815062 AN: 1461192 Hom.: 230045 Cov.: 55 AF XY: 0.562 AC XY: 408280 AN XY: 726904

African (AFR) AF: 0.372 AC: 12436 AN: 33444

American (AMR) AF: 0.646 AC: 28871 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 16836 AN: 26106

East Asian (EAS) AF: 0.662 AC: 26264 AN: 39696

South Asian (SAS) AF: 0.644 AC: 55506 AN: 86248

European-Finnish (FIN) AF: 0.394 AC: 20886 AN: 53030

Middle Eastern (MID) AF: 0.677 AC: 3905 AN: 5768

European-Non Finnish (NFE) AF: 0.554 AC: 616351 AN: 1111820

Other (OTH) AF: 0.563 AC: 34007 AN: 60388

GnomAD4 genome AF: 0.510 AC: 77532 AN: 152100 Hom.: 20646 Cov.: 34 AF XY: 0.504 AC XY: 37494 AN XY: 74360

African (AFR) AF: 0.374 AC: 15507 AN: 41496

American (AMR) AF: 0.593 AC: 9078 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2233 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3239 AN: 5148

South Asian (SAS) AF: 0.662 AC: 3196 AN: 4828

European-Finnish (FIN) AF: 0.377 AC: 3988 AN: 10580

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38187 AN: 67958

Other (OTH) AF: 0.562 AC: 1186 AN: 2112

Alfa AF: 0.564 Hom.: 53385

Bravo AF: 0.523

TwinsUK AF: 0.556 AC: 2063

ALSPAC AF: 0.543 AC: 2091

ESP6500AA AF: 0.367 AC: 1618

ESP6500EA AF: 0.567 AC: 4873

ExAC AF: 0.561 AC: 68172

Asia WGS AF: 0.630 AC: 2192 AN: 3478

EpiCase AF: 0.582

EpiControl AF: 0.586

ClinVar

ClinVar submissions as Germline

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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.4
DANN	Benign	0.90
DEOGEN2	Benign	0.098	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.000014	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.6
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Benign	0.36	T
Sift4G	Benign	0.36	T
Polyphen		0.19	B
Vest4		0.028
MPC		0.13
ClinPred		0.012	T
GERP RS		3.8
Varity_R		0.035
gMVP		0.33
Mutation Taster		=97/3	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: rs3746731; hg19: chr20-23065209; COSMIC: COSV55664149;