rs2122646

Positions:

• chr4-61930576-A-G
• chr4-61930576-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.2113-4264A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 151,976 control chromosomes in the GnomAD database, including 31,056 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 0.63 (31056 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.2113-4264A>G		intron_variant		ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.2113-4264A>G		intron_variant			NM_001387552.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95813 AN: 151858 Hom.: 31051 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.631 AC: 95845 AN: 151976 Hom.: 31056 Cov.: 32 AF XY: 0.622 AC XY: 46177 AN XY: 74270

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.645

Alfa AF: 0.674 Hom.: 4181

Bravo AF: 0.618

Asia WGS AF: 0.453 AC: 1574 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.22

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: rs2122646; hg19: chr4-62796294;