rs12503398

Positions:

• chr4-61912597-A-G
• chr4-61912597-A-T

Variant summary

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

The NM_001387552.1(ADGRL3):​c.2074-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 804,254 control chromosomes in the GnomAD database, including 37,489 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 0.27 (6306 hom., cov: 32)
  • Exomes 𝑓: 0.30 (31183 hom.)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.2074-122A>G		intron_variant		ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.2074-122A>G		intron_variant			NM_001387552.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41479 AN: 151860 Hom.: 6308 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.302 AC: 196682 AN: 652276 Hom.: 31183 AF XY: 0.304 AC XY: 103592 AN XY: 341198

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.335

Gnomad4 EAS exome AF: 0.471

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.273 AC: 41498 AN: 151978 Hom.: 6306 Cov.: 32 AF XY: 0.282 AC XY: 20914 AN XY: 74278

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.255

Alfa AF: 0.266 Hom.: 923

Bravo AF: 0.269

Asia WGS AF: 0.382 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.61

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: rs12503398; hg19: chr4-62778315; COSMIC: COSV72230059;