rs748448343

Variant names:

• chr4-62070654-G-A
• rs748448343
• NM_001387552.1:c.4378G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-62070654-G-A
• chr4-62070654-G-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001387552.1(ADGRL3):​c.4378G>A​(p.Ala1460Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,551,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: ADGRL3 NM_001387552.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 0 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]

ADGRL3-AS1 (HGNC:50604): (ADGRL3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.105930656).
• BS2: High AC in GnomAd4 at 10 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.4378G>A	p.Ala1460Thr	missense	Exon 27 of 27	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.4360G>A	p.Ala1454Thr	missense	Exon 26 of 26	NP_001309331.1
	ADGRL3	NM_001371344.2		c.4333G>A	p.Ala1445Thr	missense	Exon 24 of 24	NP_001358273.1	E7EVD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.4378G>A	p.Ala1460Thr	missense	Exon 27 of 27	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.*485G>A		3_prime_UTR	Exon 26 of 26	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.4489G>A	p.Ala1497Thr	missense	Exon 25 of 25	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152000 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000389 AC: 6 AN: 154152 AF XY: 0.0000610

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000127 AC: 178 AN: 1399302 Hom.: 0 Cov.: 32 AF XY: 0.000119 AC XY: 82 AN XY: 690160

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.000158 AC: 171 AN: 1078962

Other (OTH) AF: 0.000121 AC: 7 AN: 58000

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152000 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74246

African (AFR) AF: 0.0000483 AC: 2 AN: 41392

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000411 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.0029	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
PhyloP100		3.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.056
Sift	Benign	0.41	T
Sift4G	Benign	0.56	T
Vest4		0.080
MutPred		0.38		Gain of glycosylation at A1386 (P = 0.0076)
MVP		0.13
MPC		0.29
ClinPred		0.11	T
GERP RS		5.4
gMVP		0.22
Mutation Taster		=73/27	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: rs748448343; hg19: chr4-62936372;