Variant chr1-78893178-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022159.4(ADGRL4):c.1761G>C(p.Leu587Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000689 in 1,596,274 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ADGRL4
NM_022159.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.85

Variant links:

Genes affected

ADGRL4 (HGNC:20822): (adhesion G protein-coupled receptor L4) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in adenylate cyclase-activating G protein-coupled receptor signaling pathway. Predicted to be located in cytoplasmic vesicle and plasma membrane. Predicted to be integral component of plasma membrane. Biomarker of glioblastoma and hypertrophic cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

ADGRL4 links:

ADGRL4 (HGNC:):

ADGRL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.27778882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL4	NM_022159.4 linkuse as main transcript	c.1761G>C	p.Leu587Phe	missense_variant	13/15	ENST00000370742.4	NP_071442.2	Q9HBW9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL4	ENST00000370742.4 linkuse as main transcript	c.1761G>C	p.Leu587Phe	missense_variant	13/15	1	NM_022159.4	ENSP00000359778.3		Q9HBW9

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151470

Hom.:

Cov.:

show subpopulations

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:

0.00321

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000554

AC:

AN:

1444804

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

718826

show subpopulations

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:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151470

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73936

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.1761G>C (p.L587F) alteration is located in exon 13 (coding exon 13) of the ADGRL4 gene. This alteration results from a G to C substitution at nucleotide position 1761, causing the leucine (L) at amino acid position 587 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.10

Sift

Benign

0.074

T;D

Sift4G

Uncertain

0.055

T;T

Polyphen

0.011

.;B

Vest4

0.56

MutPred

0.66

.;Loss of catalytic residue at L587 (P = 0.1256);

MVP

0.49

MPC

0.051

ClinPred

0.77

GERP RS

5.3

Varity_R

0.26

gMVP

0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over