dbSNP rs1505666: ADGRL3:c.-712A>G (chr4-61201293-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001387552.1(ADGRL3):c.-712A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 153,598 control chromosomes in the GnomAD database, including 31,195 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 0.63 ( 30823 hom., cov: 32)

Exomes 𝑓: 0.67 ( 372 hom. )

Consequence

ADGRL3
NM_001387552.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.280

Publications

2 publications found

Variant links:

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]

ADGRL3 links:

LOC124900173 (HGNC:):

LOC124900173 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1 link	c.-712A>G		5_prime_UTR_variant	Exon 1 of 27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1 link	c.-712A>G		5_prime_UTR_variant	Exon 1 of 27		NM_001387552.1	ENSP00000507980.1		A0A804HKL8
ADGRL3	ENST00000512091.6 link	c.-712A>G		5_prime_UTR_variant	Exon 1 of 26	1		ENSP00000423388.1		Q9HAR2-2

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96093

AN:

151836

Hom.:

30813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.528

Gnomad AMI

AF:

0.537

Gnomad AMR

AF:

0.703

Gnomad ASJ

AF:

0.755

Gnomad EAS

AF:

0.678

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.639

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.673

Gnomad OTH

AF:

0.630

GnomAD4 exome

AF:

0.670

AC:

1103

AN:

1646

Hom.:

372

Cov.:

AF XY:

0.667

AC XY:

734

AN XY:

1100

show subpopulations

African (AFR)

AF:

0.538

AC:

AN:

American (AMR)

AF:

0.833

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AF:

0.655

AC:

245

AN:

374

European-Finnish (FIN)

AF:

0.657

AC:

284

AN:

432

Middle Eastern (MID)

AF:

0.667

AC:

AN:

European-Non Finnish (NFE)

AF:

0.683

AC:

497

AN:

728

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.633

AC:

96143

AN:

151952

Hom.:

30823

Cov.:

AF XY:

0.630

AC XY:

46824

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.528

AC:

21875

AN:

41458

American (AMR)

AF:

0.703

AC:

10747

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.755

AC:

2622

AN:

3472

East Asian (EAS)

AF:

0.677

AC:

3468

AN:

5124

South Asian (SAS)

AF:

0.614

AC:

2950

AN:

4806

European-Finnish (FIN)

AF:

0.639

AC:

6751

AN:

10570

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.673

AC:

45684

AN:

67928

Other (OTH)

AF:

0.633

AC:

1336

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1835

3671

5506

7342

9177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.641

Hom.:

4374

Bravo

AF:

0.636

Asia WGS

AF:

0.640

AC:

2223

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.1

(source)

DANN

Benign

0.53

PhyloP100

-0.28

PromoterAI

0.0089

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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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