Variant chr4-61732830-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001387552.1(ADGRL3):c.675G>A(p.Ala225Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,611,820 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 28 hom. )

Consequence

ADGRL3
NM_001387552.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.220

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 4-61732830-G-A is Benign according to our data. Variant chr4-61732830-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654778.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.22 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00366 (5336/1459596) while in subpopulation MID AF= 0.0194 (112/5766). AF 95% confidence interval is 0.0165. There are 28 homozygotes in gnomad4_exome. There are 2807 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 406 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1 linkuse as main transcript	c.675G>A	p.Ala225Ala	synonymous_variant	8/27	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.675G>A	p.Ala225Ala	synonymous_variant	8/27		NM_001387552.1	ENSP00000507980.1		A0A804HKL8

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00622

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00432

AC:

1059

AN:

244940

Hom.:

AF XY:

0.00476

AC XY:

632

AN XY:

132848

show subpopulations

Gnomad AFR exome

AF:

0.000593

Gnomad AMR exome

AF:

0.00366

Gnomad ASJ exome

AF:

0.0207

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00839

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.00369

Gnomad OTH exome

AF:

0.00875

GnomAD4 exome

AF:

0.00366

AC:

5336

AN:

1459596

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

2807

AN XY:

725900

show subpopulations

Gnomad4 AFR exome

AF:

0.000927

Gnomad4 AMR exome

AF:

0.00370

Gnomad4 ASJ exome

AF:

0.0229

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00848

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00305

Gnomad4 OTH exome

AF:

0.00478

GnomAD4 genome

AF:

0.00267

AC:

406

AN:

152224

Hom.:

Cov.:

AF XY:

0.00243

AC XY:

181

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00321

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00396

Hom.:

Bravo

AF:

0.00289

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ADGRL3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.3

DANN

Benign

0.64

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over