chr4-61530685-T-C

Variant names:

• chr4-61530685-T-C
• rs335302
• NM_001387552.1:c.259+13167T>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+13167T>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 152,092 control chromosomes in the GnomAD database, including 47,726 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 (47726 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.642
• Publications: 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.259+13167T>C		intron_variant	Intron 4 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.259+13167T>C		intron_variant	Intron 4 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120032 AN: 151974 Hom.: 47672 Cov.: 32

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.790 AC: 120143 AN: 152092 Hom.: 47726 Cov.: 32 AF XY: 0.793 AC XY: 58964 AN XY: 74354

African (AFR) AF: 0.841 AC: 34892 AN: 41500

American (AMR) AF: 0.696 AC: 10628 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2509 AN: 3468

East Asian (EAS) AF: 0.936 AC: 4830 AN: 5162

South Asian (SAS) AF: 0.860 AC: 4150 AN: 4824

European-Finnish (FIN) AF: 0.806 AC: 8512 AN: 10566

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52043 AN: 67982

Other (OTH) AF: 0.776 AC: 1639 AN: 2112

Alfa AF: 0.764 Hom.: 7265

Bravo AF: 0.781

Asia WGS AF: 0.883 AC: 3072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.53
PhyloP100		-0.64
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: rs335302; hg19: chr4-62396403;