rs228545

Positions:

• chr1-79195699-G-A
• chr1-79195699-G-C

Variant summary

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

The ENST00000655029.1(ADGRL4):​c.-338+40754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,976 control chromosomes in the GnomAD database, including 24,480 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 0.56 (24480 hom., cov: 32)
• Consequence: ADGRL4 ENST00000655029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL4	ENST00000655029.1	c.-338+40754C>T		intron_variant				ENSP00000499618
ADGRL4	ENST00000661030.1	c.-337-82549C>T		intron_variant				ENSP00000499792
ADGRL4	ENST00000662895.1	c.-305+40754C>T		intron_variant, NMD_transcript_variant				ENSP00000499579

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85277 AN: 151858 Hom.: 24434 Cov.: 32

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.562 AC: 85384 AN: 151976 Hom.: 24480 Cov.: 32 AF XY: 0.562 AC XY: 41761 AN XY: 74286

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.463

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.540

Alfa AF: 0.530 Hom.: 2698

Bravo AF: 0.568

Asia WGS AF: 0.760 AC: 2642 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.2
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs228545; hg19: chr1-79661384;