1-81520773-C-T

Variant names:

• chr1-81520773-C-T
• rs11163323
• ENST00000370725.5:c.-247-60103C>T

Variant summary

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

The ENST00000370725.5(ADGRL2):​c.-247-60103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 152,026 control chromosomes in the GnomAD database, including 16,059 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 0.39 (16059 hom., cov: 32)
• Consequence: ADGRL2 ENST00000370725.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 0 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]

ENSG00000234953 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL2	NM_001366003.2	c.-309-60103C>T		intron_variant	Intron 3 of 27		NP_001352932.1
ADGRL2	NM_001366004.2	c.-309-60103C>T		intron_variant	Intron 3 of 27		NP_001352933.1
ADGRL2	NM_001393349.1	c.-247-60103C>T		intron_variant	Intron 2 of 25		NP_001380278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000370725.5	c.-247-60103C>T		intron_variant	Intron 2 of 25	5		ENSP00000359760.1
ADGRL2	ENST00000370723.5	c.-247-60103C>T		intron_variant	Intron 2 of 24	5		ENSP00000359758.1
ADGRL2	ENST00000370728.5	c.-247-60103C>T		intron_variant	Intron 2 of 24	5		ENSP00000359763.1
ADGRL2	ENST00000370727.5	c.-247-60103C>T		intron_variant	Intron 2 of 24	5		ENSP00000359762.1
ADGRL2	ENST00000370730.5	c.-247-60103C>T		intron_variant	Intron 2 of 23	5		ENSP00000359765.1
ADGRL2	ENST00000370721.5	c.-247-60103C>T		intron_variant	Intron 2 of 24	5		ENSP00000359756.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59564 AN: 151906 Hom.: 16019 Cov.: 32

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.392 AC: 59654 AN: 152026 Hom.: 16059 Cov.: 32 AF XY: 0.392 AC XY: 29116 AN XY: 74320

African (AFR) AF: 0.763 AC: 31623 AN: 41446

American (AMR) AF: 0.351 AC: 5360 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3470

East Asian (EAS) AF: 0.470 AC: 2424 AN: 5152

South Asian (SAS) AF: 0.393 AC: 1893 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2187 AN: 10572

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 14123 AN: 68002

Other (OTH) AF: 0.372 AC: 784 AN: 2110

Alfa AF: 0.305 Hom.: 1282

Bravo AF: 0.422

Asia WGS AF: 0.437 AC: 1519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.43
DANN	Benign	0.55
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: rs11163323; hg19: chr1-81986458;