rs2132074

Positions:

• chr4-61550781-G-A

Variant summary

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

The NM_001387552.1(ADGRL3):​c.259+33263G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,780 control chromosomes in the GnomAD database, including 10,961 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 0.37 (10961 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.259+33263G>A		intron_variant		ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.259+33263G>A		intron_variant			NM_001387552.1	ENSP00000507980

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56146 AN: 151662 Hom.: 10954 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.370 AC: 56181 AN: 151780 Hom.: 10961 Cov.: 32 AF XY: 0.378 AC XY: 28017 AN XY: 74166

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.368

Alfa AF: 0.336 Hom.: 11633

Bravo AF: 0.371

Asia WGS AF: 0.611 AC: 2121 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.21

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: rs2132074; hg19: chr4-62416499;