rs6551665

Positions:

• chr4-61873823-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.1481-18833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,506 control chromosomes in the GnomAD database, including 26,963 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 0.59 (26963 hom., cov: 29)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.1481-18833G>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.1481-18833G>A		intron_variant			NM_001387552.1	ENSP00000507980

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89494 AN: 151388 Hom.: 26951 Cov.: 29

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.591 AC: 89547 AN: 151506 Hom.: 26963 Cov.: 29 AF XY: 0.598 AC XY: 44263 AN XY: 73972

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.599

Alfa AF: 0.610 Hom.: 52043

Bravo AF: 0.588

Asia WGS AF: 0.650 AC: 2258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.26

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: rs6551665; hg19: chr4-62739541;