rs7525345

chr1-78900696-G-A

Variant summary

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

The NM_022159.4(ADGRL4):c.1750-7507C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,120 control chromosomes in the GnomAD database, including 155 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 0.039 (155 hom., cov: 32)
• Consequence: ADGRL4 NM_022159.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRL4	NM_022159.4	c.1750-7507C>T		intron_variant		ENST00000370742.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRL4	ENST00000370742.4	c.1750-7507C>T		intron_variant		1	NM_022159.4	P1

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5921 AN: 152002 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0423

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.000968

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0389 AC: 5925 AN: 152120 Hom.: 155 Cov.: 32 AF XY: 0.0381 AC XY: 2830 AN XY: 74364

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.0363

Gnomad4 NFE AF: 0.0536

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0498 Hom.: 99

Bravo AF: 0.0390

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.64

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: rs7525345; hg19: chr1-79366381; COSMIC: COSV66060450;