rs2343250

Variant names:

• chr4-61606964-A-G
• rs2343250
• NM_001387552.1:c.473+19524A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-61606964-A-G
• chr4-61606964-A-T

Variant summary

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

The NM_001387552.1(ADGRL3):​c.473+19524A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,930 control chromosomes in the GnomAD database, including 32,798 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 0.64 (32798 hom., cov: 31)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563
• Publications: 2 publications found

Genes affected

ADGRL3 (HGNC:20974): (adhesion G protein-coupled receptor L3) This gene encodes a member of the latrophilin subfamily of G-protein coupled receptors (GPCR). Latrophilins may function in both cell adhesion and signal transduction. In experiments with non-human species, endogenous proteolytic cleavage within a cysteine-rich GPS (G-protein-coupled-receptor proteolysis site) domain resulted in two subunits (a large extracellular N-terminal cell adhesion subunit and a subunit with substantial similarity to the secretin/calcitonin family of GPCRs) being non-covalently bound at the cell membrane. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387552.1. 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
	ADGRL3	NM_001387552.1	MANE Select	c.473+19524A>G		intron	N/A	NP_001374481.1
	ADGRL3	NM_001322402.3		c.473+19524A>G		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.473+19524A>G		intron	N/A	NP_001358273.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.473+19524A>G		intron	N/A	ENSP00000507980.1
	ADGRL3	ENST00000512091.6	TSL:1	c.269+19524A>G		intron	N/A	ENSP00000423388.1
	ADGRL3	ENST00000506720.5	TSL:5	c.473+19524A>G		intron	N/A	ENSP00000420931.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96539 AN: 151812 Hom.: 32733 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.636 AC: 96659 AN: 151930 Hom.: 32798 Cov.: 31 AF XY: 0.641 AC XY: 47558 AN XY: 74244

African (AFR) AF: 0.857 AC: 35551 AN: 41460

American (AMR) AF: 0.638 AC: 9723 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1898 AN: 3470

East Asian (EAS) AF: 0.915 AC: 4697 AN: 5136

South Asian (SAS) AF: 0.553 AC: 2666 AN: 4818

European-Finnish (FIN) AF: 0.575 AC: 6067 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.504 AC: 34207 AN: 67930

Other (OTH) AF: 0.605 AC: 1280 AN: 2114

Alfa AF: 0.530 Hom.: 6933

Bravo AF: 0.656

Asia WGS AF: 0.763 AC: 2653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.5
DANN	Benign	0.83
PhyloP100		-0.56
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: rs2343250; hg19: chr4-62472682;