chr1-81946916-G-A

Variant names:

• chr1-81946916-G-A
• rs3790889
• NM_001366006.2:c.1210+3147G>A

Variant summary

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

The NM_001366006.2(ADGRL2):​c.1210+3147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,930 control chromosomes in the GnomAD database, including 11,409 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 0.38 (11409 hom., cov: 31)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL2	NM_001366006.2	c.1210+3147G>A		intron_variant	Intron 6 of 23	ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000686636.1	c.1210+3147G>A		intron_variant	Intron 6 of 23		NM_001366006.2	ENSP00000509478.1
ADGRL2	ENST00000370725.5	c.1198+3147G>A		intron_variant	Intron 8 of 25	5		ENSP00000359760.1
ADGRL2	ENST00000370723.5	c.1198+3147G>A		intron_variant	Intron 8 of 24	5		ENSP00000359758.1
ADGRL2	ENST00000370728.5	c.1198+3147G>A		intron_variant	Intron 8 of 24	5		ENSP00000359763.1
ADGRL2	ENST00000370727.5	c.1198+3147G>A		intron_variant	Intron 8 of 24	5		ENSP00000359762.1
ADGRL2	ENST00000370730.5	c.1198+3147G>A		intron_variant	Intron 8 of 23	5		ENSP00000359765.1
ADGRL2	ENST00000370721.5	c.1210+3147G>A		intron_variant	Intron 9 of 24	5		ENSP00000359756.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57927 AN: 151812 Hom.: 11399 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.382 AC: 57972 AN: 151930 Hom.: 11409 Cov.: 31 AF XY: 0.381 AC XY: 28253 AN XY: 74234

African (AFR) AF: 0.352 AC: 14590 AN: 41448

American (AMR) AF: 0.316 AC: 4817 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1400 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1314 AN: 5162

South Asian (SAS) AF: 0.381 AC: 1837 AN: 4822

European-Finnish (FIN) AF: 0.440 AC: 4643 AN: 10548

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27864 AN: 67910

Other (OTH) AF: 0.388 AC: 821 AN: 2114

Alfa AF: 0.395 Hom.: 9093

Bravo AF: 0.371

Asia WGS AF: 0.318 AC: 1108 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.26
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: rs3790889; hg19: chr1-82412600;