chr1-81422920-G-A

Variant names:

• chr1-81422920-G-A
• rs10874241
• ENST00000370725.5:c.-301-22116G>A

Variant summary

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

The ENST00000370725.5(ADGRL2):​c.-301-22116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,274 control chromosomes in the GnomAD database, including 67,967 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 0.94 (67967 hom., cov: 33)
• Consequence: ADGRL2 ENST00000370725.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370725.5. 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
	ADGRL2	NM_001366003.2		c.-378-22101G>A		intron	N/A	NP_001352932.1
	ADGRL2	NM_001366004.2		c.-379+8569G>A		intron	N/A	NP_001352933.1
	ADGRL2	NM_001393349.1		c.-316-22101G>A		intron	N/A	NP_001380278.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	ENST00000370725.5	TSL:5	c.-301-22116G>A		intron	N/A	ENSP00000359760.1
	ADGRL2	ENST00000370723.5	TSL:5	c.-301-22116G>A		intron	N/A	ENSP00000359758.1
	ADGRL2	ENST00000370728.5	TSL:5	c.-301-22116G>A		intron	N/A	ENSP00000359763.1

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143360 AN: 152156 Hom.: 67923 Cov.: 33

Gnomad AFR AF: 0.826

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.942 AC: 143458 AN: 152274 Hom.: 67967 Cov.: 33 AF XY: 0.944 AC XY: 70257 AN XY: 74460

African (AFR) AF: 0.826 AC: 34306 AN: 41520

American (AMR) AF: 0.972 AC: 14877 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3453 AN: 3472

East Asian (EAS) AF: 0.955 AC: 4938 AN: 5172

South Asian (SAS) AF: 0.966 AC: 4665 AN: 4828

European-Finnish (FIN) AF: 0.993 AC: 10542 AN: 10616

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.991 AC: 67448 AN: 68048

Other (OTH) AF: 0.961 AC: 2031 AN: 2114

Alfa AF: 0.977 Hom.: 113852

Bravo AF: 0.935

Asia WGS AF: 0.960 AC: 3339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.3
DANN	Benign	0.68
PhyloP100		0.22
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: rs10874241; hg19: chr1-81888605; COSMIC: COSV65860587; COSMIC: COSV65860587;