Variant 19-14641513-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032571.5(ADGRE3):c.1154G>A(p.Arg385Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,613,850 control chromosomes in the GnomAD database, including 598,279 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.83 ( 53340 hom., cov: 31)

Exomes 𝑓: 0.86 ( 544939 hom. )

Consequence

ADGRE3
NM_032571.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Variant links:

Genes affected

ADGRE3 (HGNC:23647): (adhesion G protein-coupled receptor E3) This gene encodes a member of the class B seven-span transmembrane (TM7) receptor family expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain. This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 2 on chromosome 19. This protein may play a role in myeloid-myeloid interactions during immune and inflammatory responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]

ADGRE3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2887201E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRE3	NM_032571.5 linkuse as main transcript	c.1154G>A	p.Arg385Gln	missense_variant	10/16	ENST00000253673.6	NP_115960.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRE3	ENST00000253673.6 linkuse as main transcript	c.1154G>A	p.Arg385Gln	missense_variant	10/16	1	NM_032571.5	ENSP00000253673	P1	Q9BY15-1
ADGRE3	ENST00000344373.8 linkuse as main transcript	c.998G>A	p.Arg333Gln	missense_variant	9/15	1		ENSP00000340758		Q9BY15-2
ADGRE3	ENST00000443157.6 linkuse as main transcript	c.776G>A	p.Arg259Gln	missense_variant	7/13	2		ENSP00000396208
ADGRE3	ENST00000599900.5 linkuse as main transcript	c.509G>A	p.Arg170Gln	missense_variant	9/15	5		ENSP00000471853

Frequencies

GnomAD3 genomes

AF:

0.835

AC:

126945

AN:

152018

Hom.:

53309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.749

Gnomad AMI

AF:

0.885

Gnomad AMR

AF:

0.905

Gnomad ASJ

AF:

0.845

Gnomad EAS

AF:

0.859

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.845

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.859

Gnomad OTH

AF:

0.847

GnomAD3 exomes

AF:

0.869

AC:

218261

AN:

251064

Hom.:

95272

AF XY:

0.874

AC XY:

118581

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.746

Gnomad AMR exome

AF:

0.932

Gnomad ASJ exome

AF:

0.856

Gnomad EAS exome

AF:

0.868

Gnomad SAS exome

AF:

0.947

Gnomad FIN exome

AF:

0.850

Gnomad NFE exome

AF:

0.852

Gnomad OTH exome

AF:

0.874

GnomAD4 exome

AF:

0.863

AC:

1261354

AN:

1461714

Hom.:

544939

Cov.:

AF XY:

0.865

AC XY:

629269

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.745

Gnomad4 AMR exome

AF:

0.928

Gnomad4 ASJ exome

AF:

0.850

Gnomad4 EAS exome

AF:

0.859

Gnomad4 SAS exome

AF:

0.945

Gnomad4 FIN exome

AF:

0.849

Gnomad4 NFE exome

AF:

0.859

Gnomad4 OTH exome

AF:

0.862

GnomAD4 genome

AF:

0.835

AC:

127026

AN:

152136

Hom.:

53340

Cov.:

AF XY:

0.837

AC XY:

62263

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.748

Gnomad4 AMR

AF:

0.905

Gnomad4 ASJ

AF:

0.845

Gnomad4 EAS

AF:

0.859

Gnomad4 SAS

AF:

0.951

Gnomad4 FIN

AF:

0.845

Gnomad4 NFE

AF:

0.859

Gnomad4 OTH

AF:

0.844

Alfa

AF:

0.864

Hom.:

37389

Bravo

AF:

0.835

ESP6500AA

AF:

0.756

AC:

3332

ESP6500EA

AF:

0.857

AC:

7368

ExAC

AF:

0.864

AC:

104909

Asia WGS

AF:

0.891

AC:

3099

AN:

3478

EpiCase

AF:

0.858

EpiControl

AF:

0.849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.36

DEOGEN2

Benign

0.0057

.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.35

T;T;T;T

MetaRNN

Benign

0.0000013

T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

3.4

N;N;.;N

REVEL

Benign

0.082

Sift

Benign

1.0

T;T;.;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0050

B;B;.;B

Vest4

0.074

MPC

0.16

ClinPred

0.0052

GERP RS

2.8

Varity_R

0.037

gMVP

0.20

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over