1-78920193-T-G

Variant names:

• chr1-78920193-T-G
• rs751140928
• NM_022159.4:c.1451A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022159.4(ADGRL4):​c.1451A>C​(p.Asn484Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N484S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRL4 NM_022159.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07862005).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022159.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL4	NM_022159.4	MANE Select	c.1451A>C	p.Asn484Thr	missense	Exon 10 of 15	NP_071442.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL4	ENST00000370742.4	TSL:1 MANE Select	c.1451A>C	p.Asn484Thr	missense	Exon 10 of 15	ENSP00000359778.3	Q9HBW9
	ADGRL4	ENST00000954023.1		c.1481A>C	p.Asn494Thr	missense	Exon 10 of 15	ENSP00000624082.1
	ADGRL4	ENST00000870763.1		c.1451A>C	p.Asn484Thr	missense	Exon 10 of 14	ENSP00000540822.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.59
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.96	T
PhyloP100		2.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.084
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.34
MutPred		0.52		Gain of catalytic residue at N484 (P = 0.0207)
MVP		0.092
MPC		0.042
ClinPred		0.065	T
GERP RS		3.9
Varity_R		0.13
gMVP		0.65
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs751140928; hg19: chr1-79385878;