rs4860425

chr4-61677239-C-Achr4-61677239-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387552.1(ADGRL3):c.583+304C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 315,554 control chromosomes in the GnomAD database, including 5,244 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2386 hom., cov: 32)
  • Exomes 𝑓: 0.17 (2858 hom.)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.583+304C>A		intron_variant		ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.583+304C>A		intron_variant			NM_001387552.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26143 AN: 151370 Hom.: 2384 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.175 AC: 28711 AN: 164068 Hom.: 2858 Cov.: 0 AF XY: 0.174 AC XY: 15676 AN XY: 90336

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.228

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.173 AC: 26157 AN: 151486 Hom.: 2386 Cov.: 32 AF XY: 0.176 AC XY: 13003 AN XY: 73972

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.164

Alfa AF: 0.173 Hom.: 2496

Bravo AF: 0.169

Asia WGS AF: 0.137 AC: 475 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.13
Dann	Benign	0.27

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: rs4860425; hg19: chr4-62542957; COSMIC: COSV72268572;