Genetic Variant ADGRL1:p.Glu1416Glu (chr19-14151035-T-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_014921.5(ADGRL1):c.4248A>G(p.Glu1416Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ADGRL1
NM_014921.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.600

Publications

0 publications found

Variant links:

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 links:

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

ADGRL1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP7

Synonymous conserved (PhyloP=0.6 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRL1	NM_014921.5	MANE Select	c.4248A>G	p.Glu1416Glu	synonymous	Exon 23 of 23	NP_055736.2
ADGRL1	NM_001008701.3		c.4263A>G	p.Glu1421Glu	synonymous	Exon 24 of 24	NP_001008701.1	O94910-1
ADGRL1-AS1	NR_045214.1		n.73-4117T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRL1	ENST00000361434.8	TSL:1 MANE Select	c.4248A>G	p.Glu1416Glu	synonymous	Exon 23 of 23	ENSP00000355328.2	O94910-2
ADGRL1	ENST00000340736.10	TSL:1	c.4263A>G	p.Glu1421Glu	synonymous	Exon 24 of 24	ENSP00000340688.5	O94910-1
ADGRL1-AS1	ENST00000588387.3	TSL:1	n.80-4117T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

140454

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

117544

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1115128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

542812

African (AFR)

AF:

0.00

AC:

AN:

24292

American (AMR)

AF:

0.00

AC:

AN:

24122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13630

East Asian (EAS)

AF:

0.00

AC:

AN:

15310

South Asian (SAS)

AF:

0.00

AC:

AN:

71346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2698

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

897146

Other (OTH)

AF:

0.00

AC:

AN:

40394

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

140454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68094

African (AFR)

AF:

0.00

AC:

AN:

39076

American (AMR)

AF:

0.00

AC:

AN:

14338

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3296

East Asian (EAS)

AF:

0.00

AC:

AN:

4024

South Asian (SAS)

AF:

0.00

AC:

AN:

3764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64002

Other (OTH)

AF:

0.00

AC:

AN:

1982

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.0

(source)

DANN

Benign

0.39

PhyloP100

0.60

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over