rs2345039

Variant names:

• chr4-61899312-G-C
• rs2345039
• NM_001387552.1:c.1887+3478G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-61899312-G-C
• chr4-61899312-G-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.1887+3478G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,400 control chromosomes in the GnomAD database, including 13,349 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 0.42 (13349 hom., cov: 30)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 21 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 (NFE) allele frequency at 95% confidence interval = 0.448 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.1887+3478G>C		intron	N/A	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.1887+3478G>C		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1887+3478G>C		intron	N/A	NP_001358273.1	E7EVD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.1887+3478G>C		intron	N/A	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.1683+3478G>C		intron	N/A	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.1887+3478G>C		intron	N/A	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63247 AN: 151282 Hom.: 13346 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.418 AC: 63261 AN: 151400 Hom.: 13349 Cov.: 30 AF XY: 0.412 AC XY: 30508 AN XY: 73960

African (AFR) AF: 0.372 AC: 15325 AN: 41188

American (AMR) AF: 0.420 AC: 6398 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1490 AN: 3466

East Asian (EAS) AF: 0.369 AC: 1889 AN: 5120

South Asian (SAS) AF: 0.325 AC: 1562 AN: 4802

European-Finnish (FIN) AF: 0.445 AC: 4663 AN: 10474

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30660 AN: 67822

Other (OTH) AF: 0.447 AC: 942 AN: 2106

Alfa AF: 0.429 Hom.: 1724

Bravo AF: 0.417

Asia WGS AF: 0.373 AC: 1299 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	0.18
DANN	Benign	0.51
PhyloP100		-1.4
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: rs2345039; hg19: chr4-62765030;