chr4-61935010-T-C

Position:

• chr4-61935010-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001387552.1(ADGRL3):​c.2283T>C​(p.Asn761Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,612,898 control chromosomes in the GnomAD database, including 437,210 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 0.74 (41749 hom., cov: 32)
  • Exomes 𝑓: 0.73 (395461 hom.)
• Consequence: ADGRL3 NM_001387552.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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]

ADGRL3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=1.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.2283T>C	p.Asn761Asn	synonymous_variant	14/27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.2283T>C	p.Asn761Asn	synonymous_variant	14/27		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112049 AN: 151890 Hom.: 41715 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.727

GnomAD3 exomes AF: 0.695 AC: 172771 AN: 248604 Hom.: 60874 AF XY: 0.693 AC XY: 93524 AN XY: 134860

Gnomad AFR exome AF: 0.797

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.681

Gnomad EAS exome AF: 0.607

Gnomad SAS exome AF: 0.626

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.712

GnomAD4 exome AF: 0.734 AC: 1071799 AN: 1460890 Hom.: 395461 Cov.: 44 AF XY: 0.730 AC XY: 530718 AN XY: 726720

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.579

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.637

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.751

Gnomad4 OTH exome AF: 0.731

GnomAD4 genome AF: 0.738 AC: 112143 AN: 152008 Hom.: 41749 Cov.: 32 AF XY: 0.730 AC XY: 54231 AN XY: 74290

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.687

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.728

Alfa AF: 0.736 Hom.: 59184

Bravo AF: 0.732

Asia WGS AF: 0.630 AC: 2192 AN: 3478

EpiCase AF: 0.743

EpiControl AF: 0.743

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.9
DANN	Benign	0.72

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: rs734644; hg19: chr4-62800728; COSMIC: COSV72231149;