NM_001387552.1:c.-239-4614G>T

Variant names:

• chr4-61378510-G-T
• rs17219773
• NM_001387552.1:c.-239-4614G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387552.1(ADGRL3):​c.-239-4614G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 151,832 control chromosomes in the GnomAD database, including 1,138 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 0.11 (1138 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 1 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 (SAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.-239-4614G>T		intron_variant	Intron 1 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-239-4614G>T		intron_variant	Intron 1 of 26		NM_001387552.1	ENSP00000507980.1
ADGRL3	ENST00000512091.6	c.-239-4614G>T		intron_variant	Intron 1 of 25	1		ENSP00000423388.1
ADGRL3	ENST00000514591.5	c.-239-4614G>T		intron_variant	Intron 1 of 24	5		ENSP00000422533.1
ADGRL3	ENST00000509779.5	n.103-4614G>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17137 AN: 151716 Hom.: 1133 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.113 AC: 17146 AN: 151832 Hom.: 1138 Cov.: 32 AF XY: 0.116 AC XY: 8610 AN XY: 74198

African (AFR) AF: 0.0340 AC: 1408 AN: 41460

American (AMR) AF: 0.101 AC: 1530 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3464

East Asian (EAS) AF: 0.141 AC: 727 AN: 5148

South Asian (SAS) AF: 0.153 AC: 737 AN: 4816

European-Finnish (FIN) AF: 0.184 AC: 1939 AN: 10550

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9839 AN: 67874

Other (OTH) AF: 0.118 AC: 249 AN: 2106

Alfa AF: 0.128 Hom.: 2301

Bravo AF: 0.101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.46
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17219773; hg19: chr4-62244228;