rs2345041

Variant names:

• chr4-61832639-G-A
• rs2345041
• NM_001387552.1:c.1480+18750G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-61832639-G-A
• chr4-61832639-G-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.1480+18750G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,788 control chromosomes in the GnomAD database, including 10,257 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 0.33 (10257 hom., cov: 31)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.1480+18750G>A		intron_variant	Intron 9 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.1480+18750G>A		intron_variant	Intron 9 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49740 AN: 151670 Hom.: 10223 Cov.: 31

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.328 AC: 49842 AN: 151788 Hom.: 10257 Cov.: 31 AF XY: 0.338 AC XY: 25076 AN XY: 74168

African (AFR) AF: 0.528 AC: 21817 AN: 41352

American (AMR) AF: 0.382 AC: 5832 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3470

East Asian (EAS) AF: 0.616 AC: 3166 AN: 5138

South Asian (SAS) AF: 0.416 AC: 2000 AN: 4812

European-Finnish (FIN) AF: 0.283 AC: 2978 AN: 10536

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12075 AN: 67926

Other (OTH) AF: 0.329 AC: 691 AN: 2100

Alfa AF: 0.210 Hom.: 6954

Bravo AF: 0.344

Asia WGS AF: 0.514 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.092
DANN	Benign	0.36
PhyloP100		-2.4
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: rs2345041; hg19: chr4-62698357;