rs10517541

Variant names:

• chr4-61570098-T-C
• rs10517541
• NM_001387552.1:c.260-17129T>C

Variant summary

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

The NM_001387552.1(ADGRL3):​c.260-17129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0485 in 152,262 control chromosomes in the GnomAD database, including 548 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 0.048 (548 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.260-17129T>C		intron_variant	Intron 4 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.260-17129T>C		intron_variant	Intron 4 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7334 AN: 152144 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0485 AC: 7380 AN: 152262 Hom.: 548 Cov.: 32 AF XY: 0.0474 AC XY: 3530 AN XY: 74462

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0237

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00121

Gnomad4 OTH AF: 0.0341

Alfa AF: 0.0288 Hom.: 41

Bravo AF: 0.0565

Asia WGS AF: 0.0180 AC: 63 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs10517541; hg19: chr4-62435816;