rs1456873

Positions:

• chr4-61436445-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.-174+53256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,000 control chromosomes in the GnomAD database, including 12,307 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 0.39 (12307 hom., cov: 33)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.-174+53256G>A		intron_variant		ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-174+53256G>A		intron_variant			NM_001387552.1
ADGRL3	ENST00000512091.6	c.-174+53256G>A		intron_variant		1
ADGRL3	ENST00000514591.5	c.-174+53256G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59794 AN: 151880 Hom.: 12302 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.393 AC: 59808 AN: 152000 Hom.: 12307 Cov.: 33 AF XY: 0.395 AC XY: 29373 AN XY: 74296

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.399

Alfa AF: 0.425 Hom.: 2195

Bravo AF: 0.379

Asia WGS AF: 0.384 AC: 1334 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.1
DANN	Benign	0.90

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1456873; hg19: chr4-62302163;