rs1456860

chr4-61374228-T-G

Variant summary

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

The NM_001387552.1(ADGRL3):c.-239-8896T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,928 control chromosomes in the GnomAD database, including 29,273 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 0.62 (29273 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL3	NM_001387552.1	c.-239-8896T>G		intron_variant		ENST00000683033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-239-8896T>G		intron_variant			NM_001387552.1
ADGRL3	ENST00000512091.6	c.-239-8896T>G		intron_variant		1
ADGRL3	ENST00000514591.5	c.-239-8896T>G		intron_variant		5
ADGRL3	ENST00000509779.5	n.103-8896T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93892 AN: 151810 Hom.: 29251 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.618 AC: 93963 AN: 151928 Hom.: 29273 Cov.: 32 AF XY: 0.614 AC XY: 45597 AN XY: 74252

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.541

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.641

Alfa AF: 0.643 Hom.: 16808

Bravo AF: 0.619

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.0
Dann	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1456860; hg19: chr4-62239946;