rs1355368

chr4-61914104-A-Gchr4-61914104-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.2112+1347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,900 control chromosomes in the GnomAD database, including 29,083 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 0.61 (29083 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.2112+1347A>G		intron_variant		ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.2112+1347A>G		intron_variant			NM_001387552.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92963 AN: 151780 Hom.: 29079 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.632

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.612 AC: 92996 AN: 151900 Hom.: 29083 Cov.: 32 AF XY: 0.604 AC XY: 44845 AN XY: 74256

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.630

Alfa AF: 0.672 Hom.: 51154

Bravo AF: 0.600

Asia WGS AF: 0.449 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.34
Dann	Benign	0.39

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: rs1355368; hg19: chr4-62779822;