rs1202804312

Variant names:

• chr19-14160140-C-A
• NM_014921.5:c.1772G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-14160140-C-A
• chr19-14160140-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014921.5(ADGRL1):​c.1772G>T​(p.Arg591Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ADGRL1 NM_014921.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27762234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL1	NM_014921.5	c.1772G>T	p.Arg591Leu	missense_variant	Exon 8 of 23	ENST00000361434.8	NP_055736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL1	ENST00000361434.8	c.1772G>T	p.Arg591Leu	missense_variant	Exon 8 of 23	1	NM_014921.5	ENSP00000355328.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436918 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 709050

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.16e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Benign	0.094
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.012	D;D;D
Polyphen		0.75	P;P;.
Vest4		0.55
MutPred		0.45		Loss of MoRF binding (P = 0.0279);.;.;
MVP		0.043
MPC		1.4
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.39
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-14270952;