4-61527928-T-C

Variant names:

• chr4-61527928-T-C
• rs186750
• NM_001387552.1:c.259+10410T>C

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+10410T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,056 control chromosomes in the GnomAD database, including 47,762 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 0.79 (47762 hom., cov: 31)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 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+10410T>C		intron	N/A	NP_001374481.1
	ADGRL3	NM_001322402.3		c.259+10410T>C		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.259+10410T>C		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+10410T>C		intron	N/A	ENSP00000507980.1
	ADGRL3	ENST00000512091.6	TSL:1	c.55+30580T>C		intron	N/A	ENSP00000423388.1
	ADGRL3	ENST00000506720.5	TSL:5	c.259+10410T>C		intron	N/A	ENSP00000420931.1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120067 AN: 151938 Hom.: 47708 Cov.: 31

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.799

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.790 AC: 120178 AN: 152056 Hom.: 47762 Cov.: 31 AF XY: 0.793 AC XY: 58950 AN XY: 74302

African (AFR) AF: 0.841 AC: 34887 AN: 41486

American (AMR) AF: 0.696 AC: 10622 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2515 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4830 AN: 5160

South Asian (SAS) AF: 0.861 AC: 4142 AN: 4812

European-Finnish (FIN) AF: 0.806 AC: 8524 AN: 10580

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.766 AC: 52079 AN: 67976

Other (OTH) AF: 0.778 AC: 1641 AN: 2110

Alfa AF: 0.764 Hom.: 20132

Bravo AF: 0.782

Asia WGS AF: 0.883 AC: 3071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.75
PhyloP100		-1.2
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: rs186750; hg19: chr4-62393646;