rs35106420

Variant names:

• chr4-61892773-G-A
• rs35106420
• NM_001387552.1:c.1598G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-61892773-G-A
• chr4-61892773-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001387552.1(ADGRL3):​c.1598G>A​(p.Arg533Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0133 in 1,613,802 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0094 (10 hom., cov: 31)
  • Exomes 𝑓: 0.014 (184 hom.)
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• Publications: 14 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 (MetaRNN=0.008330405).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00944 (1436/152168) while in subpopulation NFE AF = 0.0161 (1096/68006). AF 95% confidence interval is 0.0153. There are 10 homozygotes in GnomAd4. There are 689 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1436 AD gene.

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.1598G>A	p.Arg533Gln	missense	Exon 10 of 27	NP_001374481.1
	ADGRL3	NM_001322402.3		c.1598G>A	p.Arg533Gln	missense	Exon 10 of 26	NP_001309331.1
	ADGRL3	NM_001371344.2		c.1598G>A	p.Arg533Gln	missense	Exon 9 of 24	NP_001358273.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.1598G>A	p.Arg533Gln	missense	Exon 10 of 27	ENSP00000507980.1
	ADGRL3	ENST00000512091.6	TSL:1	c.1394G>A	p.Arg465Gln	missense	Exon 9 of 26	ENSP00000423388.1
	ADGRL3	ENST00000506720.5	TSL:5	c.1598G>A	p.Arg533Gln	missense	Exon 8 of 25	ENSP00000420931.1

Frequencies

GnomAD3 genomes AF: 0.00946 AC: 1438 AN: 152050 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00283

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00934

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.0107 AC: 2664 AN: 249072 AF XY: 0.0110

Gnomad AFR exome AF: 0.00226

Gnomad AMR exome AF: 0.00417

Gnomad ASJ exome AF: 0.00368

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00590

Gnomad NFE exome AF: 0.0171

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0137 AC: 20045 AN: 1461634 Hom.: 184 Cov.: 32 AF XY: 0.0138 AC XY: 10042 AN XY: 727106

African (AFR) AF: 0.00179 AC: 60 AN: 33480

American (AMR) AF: 0.00436 AC: 195 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 99 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00997 AC: 860 AN: 86252

European-Finnish (FIN) AF: 0.00582 AC: 311 AN: 53402

Middle Eastern (MID) AF: 0.0120 AC: 69 AN: 5766

European-Non Finnish (NFE) AF: 0.0159 AC: 17715 AN: 1111810

Other (OTH) AF: 0.0122 AC: 734 AN: 60372

GnomAD4 genome AF: 0.00944 AC: 1436 AN: 152168 Hom.: 10 Cov.: 31 AF XY: 0.00926 AC XY: 689 AN XY: 74392

African (AFR) AF: 0.00282 AC: 117 AN: 41524

American (AMR) AF: 0.00471 AC: 72 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5146

South Asian (SAS) AF: 0.00935 AC: 45 AN: 4814

European-Finnish (FIN) AF: 0.00462 AC: 49 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0161 AC: 1096 AN: 68006

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.0141 Hom.: 72

Bravo AF: 0.00947

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0127 AC: 49

ESP6500AA AF: 0.00296 AC: 12

ESP6500EA AF: 0.0152 AC: 127

ExAC AF: 0.0118 AC: 1423

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0089	T
Eigen	Benign	0.035
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.91	T
PhyloP100		4.8
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.080
Sift	Benign	0.40	T
Sift4G	Benign	0.68	T
Polyphen		0.95	P
Vest4		0.44
MPC		0.34
ClinPred		0.0075	T
GERP RS		5.0
gMVP		0.44
Mutation Taster		=99/1	polymorphism

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: rs35106420; hg19: chr4-62758491; COSMIC: COSV72230712; COSMIC: COSV72230712;