rs3810256

Positions:

• chr19-14149034-G-A

Variant summary

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

The NM_014921.5(ADGRL1):​c.*1839C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,958 control chromosomes in the GnomAD database, including 969 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 0.10 (963 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6 hom.)
• Consequence: ADGRL1 NM_014921.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738

Genes affected

ADGRL1 (HGNC:20973): (adhesion G protein-coupled receptor L1) 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. Latrophilin-1 has been shown to recruit the neurotoxin from black widow spider venom, alpha-latrotoxin, to the synapse plasma membrane. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

ADGRL1-AS1 (HGNC:55309): (ADGRL1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL1	NM_014921.5	c.*1839C>T		3_prime_UTR_variant	23/23	ENST00000361434.8	NP_055736.2
ADGRL1-AS1	NR_045214.1	n.73-6118G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL1	ENST00000361434.8	c.*1839C>T		3_prime_UTR_variant	23/23	1	NM_014921.5	ENSP00000355328	A1
ADGRL1-AS1	ENST00000588387.2	n.79-6118G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15593 AN: 152040 Hom.: 961 Cov.: 32

Gnomad AFR AF: 0.0564

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0623

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.0866

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.117 AC: 94 AN: 800 Hom.: 6 Cov.: 0 AF XY: 0.107 AC XY: 57 AN XY: 534

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.0938

GnomAD4 genome AF: 0.103 AC: 15600 AN: 152158 Hom.: 963 Cov.: 32 AF XY: 0.104 AC XY: 7772 AN XY: 74384

Gnomad4 AFR AF: 0.0564

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.0623

Gnomad4 EAS AF: 0.0790

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.103

Alfa AF: 0.115 Hom.: 1370

Bravo AF: 0.107

Asia WGS AF: 0.0770 AC: 265 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3810256; hg19: chr19-14259846; COSMIC: COSV61564507; COSMIC: COSV61564507;