rs9285611

Variant names:

• chr1-81717370-C-T
• rs9285611
• ENST00000370725.5:c.-142-44441C>T

Variant summary

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

The ENST00000370725.5(ADGRL2):​c.-142-44441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,170 control chromosomes in the GnomAD database, including 2,090 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 0.16 (2090 hom., cov: 33)
• Consequence: ADGRL2 ENST00000370725.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL2	NM_001366003.2	c.-143+17562C>T		intron_variant	Intron 5 of 27		NP_001352932.1
ADGRL2	NM_001366004.2	c.-143+17562C>T		intron_variant	Intron 5 of 27		NP_001352933.1
ADGRL2	NM_001393349.1	c.-142-44441C>T		intron_variant	Intron 3 of 25		NP_001380278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000370725.5	c.-142-44441C>T		intron_variant	Intron 3 of 25	5		ENSP00000359760.1
ADGRL2	ENST00000370723.5	c.-142-44441C>T		intron_variant	Intron 3 of 24	5		ENSP00000359758.1
ADGRL2	ENST00000370728.5	c.-142-44441C>T		intron_variant	Intron 3 of 24	5		ENSP00000359763.1
ADGRL2	ENST00000370727.5	c.-142-44441C>T		intron_variant	Intron 3 of 24	5		ENSP00000359762.1
ADGRL2	ENST00000370730.5	c.-142-44441C>T		intron_variant	Intron 3 of 23	5		ENSP00000359765.1
ADGRL2	ENST00000370721.5	c.-142-44441C>T		intron_variant	Intron 3 of 24	5		ENSP00000359756.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24652 AN: 152052 Hom.: 2090 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.162 AC: 24663 AN: 152170 Hom.: 2090 Cov.: 33 AF XY: 0.164 AC XY: 12174 AN XY: 74406

African (AFR) AF: 0.141 AC: 5877 AN: 41534

American (AMR) AF: 0.108 AC: 1648 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3470

East Asian (EAS) AF: 0.104 AC: 537 AN: 5182

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4824

European-Finnish (FIN) AF: 0.179 AC: 1891 AN: 10588

Middle Eastern (MID) AF: 0.172 AC: 50 AN: 290

European-Non Finnish (NFE) AF: 0.184 AC: 12518 AN: 67986

Other (OTH) AF: 0.153 AC: 323 AN: 2114

Alfa AF: 0.174 Hom.: 4044

Bravo AF: 0.154

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.46
PhyloP100		-0.32
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: rs9285611; hg19: chr1-82183055;