4-61905175-C-T

Variant names:

• chr4-61905175-C-T
• rs6551669
• NM_001387552.1:c.1888-4385C>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.1888-4385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 151,880 control chromosomes in the GnomAD database, including 33,874 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 0.66 (33874 hom., cov: 31)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.715 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.1888-4385C>T		intron	N/A	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.1888-4385C>T		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1888-4385C>T		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.1888-4385C>T		intron	N/A	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.1684-4385C>T		intron	N/A	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.1888-4385C>T		intron	N/A	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100773 AN: 151762 Hom.: 33848 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.664 AC: 100856 AN: 151880 Hom.: 33874 Cov.: 31 AF XY: 0.660 AC XY: 48949 AN XY: 74184

African (AFR) AF: 0.582 AC: 24088 AN: 41404

American (AMR) AF: 0.645 AC: 9845 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3472

East Asian (EAS) AF: 0.551 AC: 2841 AN: 5154

South Asian (SAS) AF: 0.640 AC: 3074 AN: 4802

European-Finnish (FIN) AF: 0.727 AC: 7668 AN: 10548

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 48947 AN: 67928

Other (OTH) AF: 0.692 AC: 1461 AN: 2110

Alfa AF: 0.685 Hom.: 5420

Bravo AF: 0.653

Asia WGS AF: 0.635 AC: 2201 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.19
PhyloP100		-0.057
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: rs6551669; hg19: chr4-62770893;