Variant rs35106420 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001387552.1(ADGRL3):c.1598G>A(p.Arg533Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0133 in 1,613,802 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0094 ( 10 hom., cov: 31)

Exomes 𝑓: 0.014 ( 184 hom. )

Consequence

ADGRL3
NM_001387552.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.80

Variant links:

Genes affected

ADGRL3 (HGNC:20974): (adhesion G protein-coupled receptor L3) This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors (GPCR). Latrophilins may function in both cell adhesion and signal transduction. In experiments with non-human species, endogenous proteolytic cleavage within a cysteine-rich GPS (G-protein-coupled-receptor proteolysis site) domain resulted in two subunits (a large extracellular N-terminal cell adhesion subunit and a subunit with substantial similarity to the secretin/calcitonin family of GPCRs) being non-covalently bound at the cell membrane. [provided by RefSeq, Jul 2008]

ADGRL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008330405).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00944 (1436/152168) while in subpopulation NFE AF= 0.0161 (1096/68006). AF 95% confidence interval is 0.0153. There are 10 homozygotes in gnomad4. There are 689 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1436 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1 linkuse as main transcript	c.1598G>A	p.Arg533Gln	missense_variant	10/27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1 linkuse as main transcript	c.1598G>A	p.Arg533Gln	missense_variant	10/27		NM_001387552.1	ENSP00000507980.1		A0A804HKL8

Frequencies

GnomAD3 genomes

AF:

0.00946

AC:

1438

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00283

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.00472

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00934

Gnomad FIN

AF:

0.00462

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0107

AC:

2664

AN:

249072

Hom.:

AF XY:

0.0110

AC XY:

1484

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.00417

Gnomad ASJ exome

AF:

0.00368

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0104

Gnomad FIN exome

AF:

0.00590

Gnomad NFE exome

AF:

0.0171

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0137

AC:

20045

AN:

1461634

Hom.:

184

Cov.:

AF XY:

0.0138

AC XY:

10042

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00436

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00997

Gnomad4 FIN exome

AF:

0.00582

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00944

AC:

1436

AN:

152168

Hom.:

Cov.:

AF XY:

0.00926

AC XY:

689

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.00282

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00935

Gnomad4 FIN

AF:

0.00462

Gnomad4 NFE

AF:

0.0161

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.00947

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00296

AC:

ESP6500EA

AF:

0.0152

AC:

127

ExAC

AF:

0.0118

AC:

1423

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

.;.;.;T;T;T;.;T;.;T;T;T;T;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0083

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.1

N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.080

Sift

Benign

0.40

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.68

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.95

P;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.44

MPC

0.34

ClinPred

0.0075

GERP RS

5.0

gMVP

0.44

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