rs3828121

Variant names:

• chr1-81956516-A-G
• rs3828121
• NM_001366006.2:c.2017+456A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-81956516-A-G
• chr1-81956516-A-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001366006.2(ADGRL2):​c.2017+456A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,126 control chromosomes in the GnomAD database, including 2,725 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 0.15 (2725 hom., cov: 32)
• Consequence: ADGRL2 NM_001366006.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366006.2. 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_001366006.2	MANE Select	c.2017+456A>G		intron	N/A	NP_001352935.1
	ADGRL2	NM_001437671.1		c.*448A>G		3_prime_UTR	Exon 9 of 9	NP_001424600.1
	ADGRL2	NM_001366005.2		c.2017+456A>G		intron	N/A	NP_001352934.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL2	ENST00000686636.1	MANE Select	c.2017+456A>G		intron	N/A	ENSP00000509478.1
	ADGRL2	ENST00000370725.5	TSL:5	c.2005+456A>G		intron	N/A	ENSP00000359760.1
	ADGRL2	ENST00000370723.5	TSL:5	c.1966+456A>G		intron	N/A	ENSP00000359758.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22213 AN: 152008 Hom.: 2725 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.146 AC: 22218 AN: 152126 Hom.: 2725 Cov.: 32 AF XY: 0.152 AC XY: 11312 AN XY: 74338

African (AFR) AF: 0.0359 AC: 1490 AN: 41524

American (AMR) AF: 0.240 AC: 3667 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3468

East Asian (EAS) AF: 0.632 AC: 3262 AN: 5164

South Asian (SAS) AF: 0.347 AC: 1671 AN: 4822

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10592

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9966 AN: 67972

Other (OTH) AF: 0.142 AC: 300 AN: 2114

Alfa AF: 0.159 Hom.: 1207

Bravo AF: 0.151

Asia WGS AF: 0.451 AC: 1563 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		0.89
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: rs3828121; hg19: chr1-82422200;