4-61903413-G-C

Variant names:

• chr4-61903413-G-C
• rs6813183
• NM_001387552.1:c.1888-6147G>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.1888-6147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,896 control chromosomes in the GnomAD database, including 34,471 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 0.67 (34471 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.716 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.1888-6147G>C		intron	N/A	NP_001374481.1
	ADGRL3	NM_001322402.3		c.1888-6147G>C		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1888-6147G>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.1888-6147G>C		intron	N/A	ENSP00000507980.1
	ADGRL3	ENST00000512091.6	TSL:1	c.1684-6147G>C		intron	N/A	ENSP00000423388.1
	ADGRL3	ENST00000506720.5	TSL:5	c.1888-6147G>C		intron	N/A	ENSP00000420931.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101767 AN: 151778 Hom.: 34448 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.673

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.670 AC: 101845 AN: 151896 Hom.: 34471 Cov.: 32 AF XY: 0.666 AC XY: 49406 AN XY: 74206

African (AFR) AF: 0.604 AC: 25030 AN: 41432

American (AMR) AF: 0.648 AC: 9885 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2288 AN: 3466

East Asian (EAS) AF: 0.550 AC: 2821 AN: 5128

South Asian (SAS) AF: 0.639 AC: 3078 AN: 4816

European-Finnish (FIN) AF: 0.726 AC: 7640 AN: 10524

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.721 AC: 48995 AN: 67954

Other (OTH) AF: 0.694 AC: 1463 AN: 2108

Alfa AF: 0.698 Hom.: 4633

Bravo AF: 0.661

Asia WGS AF: 0.636 AC: 2214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.39
PhyloP100		-2.1
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: rs6813183; hg19: chr4-62769131;