rs12646895

Positions:

• chr4-61750462-A-G
• chr4-61750462-A-T

Variant summary

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

The NM_001387552.1(ADGRL3):​c.1399+16908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,014 control chromosomes in the GnomAD database, including 27,574 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 0.57 (27574 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.1399+16908A>G		intron_variant		ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.1399+16908A>G		intron_variant			NM_001387552.1	ENSP00000507980
	ENST00000692606.1	n.874T>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87232 AN: 151896 Hom.: 27505 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.575 AC: 87363 AN: 152014 Hom.: 27574 Cov.: 32 AF XY: 0.578 AC XY: 42976 AN XY: 74294

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.567

Alfa AF: 0.449 Hom.: 23797

Bravo AF: 0.600

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.77

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: rs12646895; hg19: chr4-62616180;