rs1505666

Positions:

• chr4-61201293-A-G
• chr4-61201293-A-T

Variant summary

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

The XM_047416555.1(LOC124900173):​c.1240A>G​(p.Lys414Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 153,598 control chromosomes in the GnomAD database, including 31,195 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (30823 hom., cov: 32)
  • Exomes 𝑓: 0.67 (372 hom.)
• Consequence: LOC124900173 XM_047416555.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

Genes affected

LOC124900173 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900173	XM_047416555.1	c.1240A>G	p.Lys414Glu	missense_variant	2/3		XP_047272511.1
ADGRL3	NM_001387552.1	c.-712A>G		5_prime_UTR_variant	1/27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-712A>G		5_prime_UTR_variant	1/27		NM_001387552.1	ENSP00000507980
ADGRL3	ENST00000512091.6	c.-712A>G		5_prime_UTR_variant	1/26	1		ENSP00000423388

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96093 AN: 151836 Hom.: 30813 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.670 AC: 1103 AN: 1646 Hom.: 372 Cov.: 0 AF XY: 0.667 AC XY: 734 AN XY: 1100

Gnomad4 AFR exome AF: 0.538

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.655

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.633 AC: 96143 AN: 151952 Hom.: 30823 Cov.: 32 AF XY: 0.630 AC XY: 46824 AN XY: 74280

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.755

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.633

Alfa AF: 0.641 Hom.: 4374

Bravo AF: 0.636

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1505666; hg19: chr4-62067011;