4-61878827-T-C

Variant names:

• chr4-61878827-T-C
• rs1947275
• NM_001387552.1:c.1481-13829T>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.1481-13829T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,064 control chromosomes in the GnomAD database, including 47,146 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 (47146 hom., cov: 31)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 11 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.82 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.1481-13829T>C		intron	N/A	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.1481-13829T>C		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1481-13829T>C		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.1481-13829T>C		intron	N/A	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.1277-13829T>C		intron	N/A	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.1481-13829T>C		intron	N/A	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119329 AN: 151946 Hom.: 47097 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.888

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.785 AC: 119433 AN: 152064 Hom.: 47146 Cov.: 31 AF XY: 0.786 AC XY: 58400 AN XY: 74328

African (AFR) AF: 0.720 AC: 29863 AN: 41472

American (AMR) AF: 0.832 AC: 12707 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2860 AN: 3470

East Asian (EAS) AF: 0.832 AC: 4290 AN: 5154

South Asian (SAS) AF: 0.841 AC: 4053 AN: 4822

European-Finnish (FIN) AF: 0.761 AC: 8036 AN: 10560

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54908 AN: 68000

Other (OTH) AF: 0.791 AC: 1668 AN: 2108

Alfa AF: 0.799 Hom.: 144742

Bravo AF: 0.783

Asia WGS AF: 0.824 AC: 2864 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.97
DANN	Benign	0.57
PhyloP100		-1.0
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: rs1947275; hg19: chr4-62744545;