rs1901223

Positions:

• chr4-61795013-G-A
• chr4-61795013-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001387552.1(ADGRL3):​c.1400-18796G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,066 control chromosomes in the GnomAD database, including 16,854 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 0.47 (16854 hom., cov: 33)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.1400-18796G>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.1400-18796G>A		intron_variant			NM_001387552.1	ENSP00000507980

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70799 AN: 151948 Hom.: 16821 Cov.: 33

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.466 AC: 70875 AN: 152066 Hom.: 16854 Cov.: 33 AF XY: 0.470 AC XY: 34925 AN XY: 74330

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.484

Alfa AF: 0.414 Hom.: 21621

Bravo AF: 0.471

Asia WGS AF: 0.545 AC: 1894 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Benign	0.47

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: rs1901223; hg19: chr4-62660731;