rs2172802

Variant names:

• chr4-61587491-A-G
• rs2172802
• NM_001387552.1:c.473+51A>G

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+51A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,258,356 control chromosomes in the GnomAD database, including 59,011 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 0.34 (9523 hom., cov: 33)
  • Exomes 𝑓: 0.28 (49488 hom.)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 17 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.473+51A>G		intron_variant	Intron 5 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.473+51A>G		intron_variant	Intron 5 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51277 AN: 151890 Hom.: 9506 Cov.: 33

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.279 AC: 308973 AN: 1106348 Hom.: 49488 AF XY: 0.279 AC XY: 155981 AN XY: 558400

African (AFR) AF: 0.417 AC: 10945 AN: 26260

American (AMR) AF: 0.554 AC: 20352 AN: 36728

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 5217 AN: 20756

East Asian (EAS) AF: 0.619 AC: 22917 AN: 37042

South Asian (SAS) AF: 0.340 AC: 23833 AN: 70198

European-Finnish (FIN) AF: 0.320 AC: 15814 AN: 49392

Middle Eastern (MID) AF: 0.285 AC: 1387 AN: 4864

European-Non Finnish (NFE) AF: 0.239 AC: 194268 AN: 813038

Other (OTH) AF: 0.296 AC: 14240 AN: 48070

GnomAD4 genome AF: 0.338 AC: 51333 AN: 152008 Hom.: 9523 Cov.: 33 AF XY: 0.347 AC XY: 25769 AN XY: 74294

African (AFR) AF: 0.418 AC: 17317 AN: 41470

American (AMR) AF: 0.441 AC: 6730 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 887 AN: 3472

East Asian (EAS) AF: 0.634 AC: 3258 AN: 5136

South Asian (SAS) AF: 0.365 AC: 1760 AN: 4828

European-Finnish (FIN) AF: 0.327 AC: 3460 AN: 10572

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16926 AN: 67960

Other (OTH) AF: 0.323 AC: 680 AN: 2108

Alfa AF: 0.295 Hom.: 14237

Bravo AF: 0.352

Asia WGS AF: 0.510 AC: 1768 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0080
DANN	Benign	0.76
PhyloP100		-1.8
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: rs2172802; hg19: chr4-62453209; COSMIC: COSV72268273;