4-61540896-G-A

Variant names:

• chr4-61540896-G-A
• rs10015239
• NM_001387552.1:c.259+23378G>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.259+23378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,874 control chromosomes in the GnomAD database, including 24,077 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 0.56 (24077 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.259+23378G>A		intron	N/A	NP_001374481.1
	ADGRL3	NM_001322402.3		c.259+23378G>A		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.259+23378G>A		intron	N/A	NP_001358273.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.259+23378G>A		intron	N/A	ENSP00000507980.1
	ADGRL3	ENST00000512091.6	TSL:1	c.55+43548G>A		intron	N/A	ENSP00000423388.1
	ADGRL3	ENST00000506720.5	TSL:5	c.259+23378G>A		intron	N/A	ENSP00000420931.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85027 AN: 151760 Hom.: 24013 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.561 AC: 85158 AN: 151874 Hom.: 24077 Cov.: 32 AF XY: 0.561 AC XY: 41617 AN XY: 74188

African (AFR) AF: 0.620 AC: 25672 AN: 41414

American (AMR) AF: 0.592 AC: 9045 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2260 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2754 AN: 5160

South Asian (SAS) AF: 0.547 AC: 2630 AN: 4810

European-Finnish (FIN) AF: 0.480 AC: 5040 AN: 10498

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35824 AN: 67948

Other (OTH) AF: 0.559 AC: 1176 AN: 2102

Alfa AF: 0.536 Hom.: 7626

Bravo AF: 0.570

Asia WGS AF: 0.585 AC: 2032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.3
DANN	Benign	0.28
PhyloP100		0.17
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: rs10015239; hg19: chr4-62406614;