rs6551665

Variant names:

• chr4-61873823-G-A
• rs6551665
• NM_001387552.1:c.1481-18833G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387552.1(ADGRL3):​c.1481-18833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,506 control chromosomes in the GnomAD database, including 26,963 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 0.59 (26963 hom., cov: 29)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629
• Publications: 41 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387552.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.1481-18833G>A		intron	N/A	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.1481-18833G>A		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1481-18833G>A		intron	N/A	NP_001358273.1	E7EVD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.1481-18833G>A		intron	N/A	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.1277-18833G>A		intron	N/A	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.1481-18833G>A		intron	N/A	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89494 AN: 151388 Hom.: 26951 Cov.: 29

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.591 AC: 89547 AN: 151506 Hom.: 26963 Cov.: 29 AF XY: 0.598 AC XY: 44263 AN XY: 73972

African (AFR) AF: 0.481 AC: 19829 AN: 41232

American (AMR) AF: 0.689 AC: 10474 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2256 AN: 3472

East Asian (EAS) AF: 0.681 AC: 3474 AN: 5104

South Asian (SAS) AF: 0.667 AC: 3197 AN: 4794

European-Finnish (FIN) AF: 0.648 AC: 6809 AN: 10500

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41359 AN: 67898

Other (OTH) AF: 0.599 AC: 1255 AN: 2096

Alfa AF: 0.604 Hom.: 81194

Bravo AF: 0.588

Asia WGS AF: 0.650 AC: 2258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		0.63
Mutation Taster		=97/3	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6551665;

hg19: chr4-62739541;