rs7525345

Variant names:

• chr1-78900696-G-A
• rs7525345
• NM_022159.4:c.1750-7507C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0521 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL4	NM_022159.4	MANE Select	c.1750-7507C>T		intron	N/A	NP_071442.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL4	ENST00000370742.4	TSL:1 MANE Select	c.1750-7507C>T		intron	N/A	ENSP00000359778.3
	ADGRL4	ENST00000655029.1		c.1615-7507C>T		intron	N/A	ENSP00000499618.1
	ADGRL4	ENST00000656841.1		c.1615-7507C>T		intron	N/A	ENSP00000499228.1

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

African (AFR) AF: 0.0154 AC: 641 AN: 41506

American (AMR) AF: 0.0422 AC: 645 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 220 AN: 3470

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5154

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4822

European-Finnish (FIN) AF: 0.0363 AC: 385 AN: 10594

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0536 AC: 3643 AN: 67986

Other (OTH) AF: 0.0488 AC: 103 AN: 2112

Alfa AF: 0.0500 Hom.: 107

Bravo AF: 0.0390

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		0.35
Mutation Taster		=100/0	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: rs7525345; hg19: chr1-79366381; COSMIC: COSV66060450;