rs12072054

Variant names:

• chr1-81777398-A-G
• rs12072054
• ENST00000370725.5:c.-101+15546A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366003.2(ADGRL2):​c.-101+15546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,186 control chromosomes in the GnomAD database, including 3,425 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 0.20 (3425 hom., cov: 33)
• Consequence: ADGRL2 NM_001366003.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.416
• Publications: 2 publications found

Genes affected

ADGRL2 (HGNC:18582): (adhesion G protein-coupled receptor L2) This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors. The encoded protein participates in the regulation of exocytosis. The proprotein is thought to be further cleaved within a cysteine-rich G-protein-coupled receptor proteolysis site into two chains that are non-covalently bound at the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366003.2. 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
	ADGRL2	NM_001366003.2		c.-101+15546A>G		intron	N/A	NP_001352932.1
	ADGRL2	NM_001366004.2		c.-101+15546A>G		intron	N/A	NP_001352933.1
	ADGRL2	NM_001393349.1		c.-101+15546A>G		intron	N/A	NP_001380278.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	ENST00000370725.5	TSL:5	c.-101+15546A>G		intron	N/A	ENSP00000359760.1	O95490-6
	ADGRL2	ENST00000370723.5	TSL:5	c.-101+15546A>G		intron	N/A	ENSP00000359758.1	O95490-7
	ADGRL2	ENST00000370728.5	TSL:5	c.-101+15546A>G		intron	N/A	ENSP00000359763.1	O95490-1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30639 AN: 152068 Hom.: 3424 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.202 AC: 30672 AN: 152186 Hom.: 3425 Cov.: 33 AF XY: 0.203 AC XY: 15094 AN XY: 74400

African (AFR) AF: 0.288 AC: 11970 AN: 41502

American (AMR) AF: 0.204 AC: 3124 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.0783 AC: 405 AN: 5174

South Asian (SAS) AF: 0.161 AC: 776 AN: 4826

European-Finnish (FIN) AF: 0.185 AC: 1958 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11466 AN: 68020

Other (OTH) AF: 0.170 AC: 358 AN: 2108

Alfa AF: 0.176 Hom.: 7256

Bravo AF: 0.203

Asia WGS AF: 0.130 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.42
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: rs12072054; hg19: chr1-82243083;