chr4-61912597-A-G

Variant names:

• chr4-61912597-A-G
• rs12503398
• NM_001387552.1:c.2074-122A>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.2074-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 804,254 control chromosomes in the GnomAD database, including 37,489 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 0.27 (6306 hom., cov: 32)
  • Exomes 𝑓: 0.30 (31183 hom.)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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.2074-122A>G		intron	N/A	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.2074-122A>G		intron	N/A	NP_001309331.1
	ADGRL3	NM_001371344.2		c.2074-122A>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.2074-122A>G		intron	N/A	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.1870-122A>G		intron	N/A	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.2074-122A>G		intron	N/A	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41479 AN: 151860 Hom.: 6308 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.302 AC: 196682 AN: 652276 Hom.: 31183 AF XY: 0.304 AC XY: 103592 AN XY: 341198

African (AFR) AF: 0.147 AC: 2379 AN: 16224

American (AMR) AF: 0.407 AC: 8982 AN: 22044

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 5695 AN: 16986

East Asian (EAS) AF: 0.471 AC: 15903 AN: 33744

South Asian (SAS) AF: 0.331 AC: 17783 AN: 53760

European-Finnish (FIN) AF: 0.321 AC: 12363 AN: 38556

Middle Eastern (MID) AF: 0.285 AC: 1063 AN: 3730

European-Non Finnish (NFE) AF: 0.283 AC: 122988 AN: 434670

Other (OTH) AF: 0.293 AC: 9526 AN: 32562

GnomAD4 genome AF: 0.273 AC: 41498 AN: 151978 Hom.: 6306 Cov.: 32 AF XY: 0.282 AC XY: 20914 AN XY: 74278

African (AFR) AF: 0.157 AC: 6501 AN: 41504

American (AMR) AF: 0.359 AC: 5473 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1175 AN: 3470

East Asian (EAS) AF: 0.475 AC: 2447 AN: 5148

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4810

European-Finnish (FIN) AF: 0.337 AC: 3556 AN: 10548

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19644 AN: 67930

Other (OTH) AF: 0.255 AC: 538 AN: 2112

Alfa AF: 0.263 Hom.: 939

Bravo AF: 0.269

Asia WGS AF: 0.382 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		1.6
Mutation Taster		=99/1	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: rs12503398; hg19: chr4-62778315; COSMIC: COSV72230059;