rs7533063

Variant names:

• chr1-78911525-A-G
• rs7533063
• NM_022159.4:c.1749+6109T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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: Benign. The variant received -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.

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.1749+6109T>C		intron	N/A	NP_071442.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL4	ENST00000370742.4	TSL:1 MANE Select	c.1749+6109T>C		intron	N/A	ENSP00000359778.3	Q9HBW9
	ADGRL4	ENST00000954023.1		c.1779+6109T>C		intron	N/A	ENSP00000624082.1
	ADGRL4	ENST00000870763.1		c.1680+6307T>C		intron	N/A	ENSP00000540822.1

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

African (AFR) AF: 0.275 AC: 11381 AN: 41396

American (AMR) AF: 0.261 AC: 3959 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1166 AN: 3464

East Asian (EAS) AF: 0.236 AC: 1214 AN: 5142

South Asian (SAS) AF: 0.225 AC: 1086 AN: 4824

European-Finnish (FIN) AF: 0.276 AC: 2912 AN: 10560

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20289 AN: 67788

Other (OTH) AF: 0.283 AC: 594 AN: 2098

Alfa AF: 0.284 Hom.: 765

Bravo AF: 0.281

Asia WGS AF: 0.226 AC: 779 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.65
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs7533063; hg19: chr1-79377210;