1-78911525-A-G

Position:

• chr1-78911525-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022159.4(ADGRL4):​c.1749+6109T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 151,632 control chromosomes in the GnomAD database, including 6,188 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 0.28 (6188 hom., cov: 32)
• Consequence: ADGRL4 NM_022159.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL4	NM_022159.4	c.1749+6109T>C		intron_variant		ENST00000370742.4	NP_071442.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL4	ENST00000370742.4	c.1749+6109T>C		intron_variant		1	NM_022159.4	ENSP00000359778	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43094 AN: 151514 Hom.: 6185 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.284

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.284 AC: 43108 AN: 151632 Hom.: 6188 Cov.: 32 AF XY: 0.281 AC XY: 20833 AN XY: 74114

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.283

Alfa AF: 0.285 Hom.: 737

Bravo AF: 0.281

Asia WGS AF: 0.226 AC: 779 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs7533063; hg19: chr1-79377210;