chr4-61374228-T-G

Variant names:

• chr4-61374228-T-G
• rs1456860
• NM_001387552.1:c.-239-8896T>G

Variant summary

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

The NM_001387552.1(ADGRL3):​c.-239-8896T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,928 control chromosomes in the GnomAD database, including 29,273 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 0.62 (29273 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.655 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.-239-8896T>G		intron	N/A	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.-239-8896T>G		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.-173-122893T>G		intron	N/A	NP_001358273.1	E7EVD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.-239-8896T>G		intron	N/A	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.-239-8896T>G		intron	N/A	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000514591.5	TSL:5	c.-239-8896T>G		intron	N/A	ENSP00000422533.1	Q9HAR2-4

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93892 AN: 151810 Hom.: 29251 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.618 AC: 93963 AN: 151928 Hom.: 29273 Cov.: 32 AF XY: 0.614 AC XY: 45597 AN XY: 74252

African (AFR) AF: 0.562 AC: 23275 AN: 41438

American (AMR) AF: 0.610 AC: 9311 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2598 AN: 3472

East Asian (EAS) AF: 0.541 AC: 2772 AN: 5128

South Asian (SAS) AF: 0.491 AC: 2360 AN: 4808

European-Finnish (FIN) AF: 0.625 AC: 6599 AN: 10550

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44878 AN: 67944

Other (OTH) AF: 0.641 AC: 1355 AN: 2114

Alfa AF: 0.645 Hom.: 18534

Bravo AF: 0.619

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.0
DANN	Benign	0.45
PhyloP100		-0.21
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: rs1456860; hg19: chr4-62239946;