chr4-61662453-A-G

Variant names:

• chr4-61662453-A-G
• rs13124636
• NM_001387552.1:c.474-14373A>G

Variant summary

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

The NM_001387552.1(ADGRL3):​c.474-14373A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 152,308 control chromosomes in the GnomAD database, including 186 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 0.041 (186 hom., cov: 33)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 2 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0602 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.474-14373A>G		intron	N/A	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.474-14373A>G		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.474-14373A>G		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.474-14373A>G		intron	N/A	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.270-14373A>G		intron	N/A	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.474-14373A>G		intron	N/A	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6247 AN: 152190 Hom.: 186 Cov.: 33

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0410 AC: 6242 AN: 152308 Hom.: 186 Cov.: 33 AF XY: 0.0407 AC XY: 3034 AN XY: 74468

African (AFR) AF: 0.0106 AC: 439 AN: 41590

American (AMR) AF: 0.0286 AC: 437 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4826

European-Finnish (FIN) AF: 0.0700 AC: 743 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0617 AC: 4199 AN: 68014

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0595 Hom.: 121

Bravo AF: 0.0368

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.24
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs13124636; hg19: chr4-62528171;