dbSNP rs3810256: ADGRL1:c.*1839C>T (chr19-14149034-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.738

Publications

16 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADGRL1	NM_014921.5 link	c.*1839C>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000361434.8	NP_055736.2	O94910-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL1	ENST00000361434.8 link	c.*1839C>T		3_prime_UTR_variant	Exon 23 of 23	1	NM_014921.5	ENSP00000355328.2		O94910-2

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15593

AN:

152040

Hom.:

961

Cov.:

show subpopulations

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:

AN:

800

Hom.:

Cov.:

AF XY:

0.107

AC XY:

AN XY:

534

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.121

AC:

AN:

446

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.116

AC:

AN:

292

Other (OTH)

AF:

0.0938

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.103

AC:

15600

AN:

152158

Hom.:

963

Cov.:

AF XY:

0.104

AC XY:

7772

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0564

AC:

2341

AN:

41528

American (AMR)

AF:

0.175

AC:

2678

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0623

AC:

216

AN:

3468

East Asian (EAS)

AF:

0.0790

AC:

407

AN:

5154

South Asian (SAS)

AF:

0.0869

AC:

419

AN:

4822

European-Finnish (FIN)

AF:

0.127

AC:

1346

AN:

10590

Middle Eastern (MID)

AF:

0.0342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.116

AC:

7863

AN:

68004

Other (OTH)

AF:

0.103

AC:

217

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

698

1396

2095

2793

3491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.115

Hom.:

1771

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

(source)

DANN

Benign

0.51

PhyloP100

0.74

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over