rs3790904

Positions:

• chr1-81916833-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366006.2(ADGRL2):​c.287+9603G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,644 control chromosomes in the GnomAD database, including 9,685 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 0.35 (9685 hom., cov: 31)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL2	NM_001366006.2	c.287+9603G>T		intron_variant		ENST00000686636.1	NP_001352935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL2	ENST00000686636.1	c.287+9603G>T		intron_variant			NM_001366006.2	ENSP00000509478

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53432 AN: 151524 Hom.: 9678 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.353 AC: 53473 AN: 151644 Hom.: 9685 Cov.: 31 AF XY: 0.353 AC XY: 26185 AN XY: 74082

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.364

Alfa AF: 0.360 Hom.: 1206

Bravo AF: 0.341

Asia WGS AF: 0.306 AC: 1054 AN: 3438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs3790904; hg19: chr1-82382517;