4-61677239-C-A

Variant names:

• chr4-61677239-C-A
• rs4860425
• NM_001387552.1:c.583+304C>A

Variant summary

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

The NM_001387552.1(ADGRL3):​c.583+304C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 315,554 control chromosomes in the GnomAD database, including 5,244 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 0.17 (2386 hom., cov: 32)
  • Exomes 𝑓: 0.17 (2858 hom.)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.583+304C>A		intron	N/A	NP_001374481.1
	ADGRL3	NM_001322402.3		c.583+304C>A		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.583+304C>A		intron	N/A	NP_001358273.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.583+304C>A		intron	N/A	ENSP00000507980.1
	ADGRL3	ENST00000512091.6	TSL:1	c.379+304C>A		intron	N/A	ENSP00000423388.1
	ADGRL3	ENST00000509089.1	TSL:3	n.487C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26143 AN: 151370 Hom.: 2384 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.175 AC: 28711 AN: 164068 Hom.: 2858 Cov.: 0 AF XY: 0.174 AC XY: 15676 AN XY: 90336

African (AFR) AF: 0.136 AC: 681 AN: 5024

American (AMR) AF: 0.242 AC: 1610 AN: 6652

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 936 AN: 4102

East Asian (EAS) AF: 0.132 AC: 1090 AN: 8272

South Asian (SAS) AF: 0.161 AC: 4305 AN: 26722

European-Finnish (FIN) AF: 0.228 AC: 1686 AN: 7380

Middle Eastern (MID) AF: 0.165 AC: 319 AN: 1930

European-Non Finnish (NFE) AF: 0.174 AC: 16578 AN: 95398

Other (OTH) AF: 0.175 AC: 1506 AN: 8588

GnomAD4 genome AF: 0.173 AC: 26157 AN: 151486 Hom.: 2386 Cov.: 32 AF XY: 0.176 AC XY: 13003 AN XY: 73972

African (AFR) AF: 0.141 AC: 5835 AN: 41372

American (AMR) AF: 0.211 AC: 3189 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3462

East Asian (EAS) AF: 0.123 AC: 632 AN: 5122

South Asian (SAS) AF: 0.157 AC: 756 AN: 4804

European-Finnish (FIN) AF: 0.240 AC: 2519 AN: 10480

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11832 AN: 67800

Other (OTH) AF: 0.164 AC: 345 AN: 2106

Alfa AF: 0.173 Hom.: 3214

Bravo AF: 0.169

Asia WGS AF: 0.137 AC: 475 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.27
PhyloP100		-1.2
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: rs4860425; hg19: chr4-62542957; COSMIC: COSV72268572;