rs2345039

Positions:

• chr4-61899312-G-C
• chr4-61899312-G-T

Variant summary

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

The NM_001387552.1(ADGRL3):​c.1887+3478G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,400 control chromosomes in the GnomAD database, including 13,349 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 0.42 (13349 hom., cov: 30)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.1887+3478G>C		intron_variant		ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.1887+3478G>C		intron_variant			NM_001387552.1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63247 AN: 151282 Hom.: 13346 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.418 AC: 63261 AN: 151400 Hom.: 13349 Cov.: 30 AF XY: 0.412 AC XY: 30508 AN XY: 73960

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.447

Alfa AF: 0.429 Hom.: 1724

Bravo AF: 0.417

Asia WGS AF: 0.373 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.51

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: rs2345039; hg19: chr4-62765030;