4-61732830-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001387552.1(ADGRL3):c.675G>A(p.Ala225=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220

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]

ACMG classification

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 GnomAd at 409 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.675G>A	p.Ala225=	synonymous_variant	8/27	ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.675G>A	p.Ala225=	synonymous_variant	8/27		NM_001387552.1

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 152106 Hom.: 3 Cov.: 32

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.: 5 AF XY: 0.00476 AC XY: 632 AN XY: 132848

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.: 28 Cov.: 30 AF XY: 0.00387 AC XY: 2807 AN XY: 725900

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.: 3 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74426

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.: 1

Bravo AF: 0.00289

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs191915391; hg19: chr4-62598548;