rs1268470454

Variant names:

• chr19-14151055-C-A
• rs1268470454
• NM_014921.5:c.4228G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-14151055-C-A
• chr19-14151055-C-G
• chr19-14151055-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_014921.5(ADGRL1):​c.4228G>T​(p.Ala1410Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1410V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000085 (0 hom.)
• Consequence: ADGRL1 NM_014921.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

Genes affected

ADGRL1 (HGNC:20973): (adhesion G protein-coupled receptor L1) 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. Latrophilin-1 has been shown to recruit the neurotoxin from black widow spider venom, alpha-latrotoxin, to the synapse plasma membrane. Alternative splicing results in multiple variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

ADGRL1-AS1 (HGNC:55309): (ADGRL1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09922111).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014921.5. 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
	ADGRL1	NM_014921.5	MANE Select	c.4228G>T	p.Ala1410Ser	missense	Exon 23 of 23	NP_055736.2
	ADGRL1	NM_001008701.3		c.4243G>T	p.Ala1415Ser	missense	Exon 24 of 24	NP_001008701.1	O94910-1
	ADGRL1-AS1	NR_045214.1		n.73-4097C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL1	ENST00000361434.8	TSL:1 MANE Select	c.4228G>T	p.Ala1410Ser	missense	Exon 23 of 23	ENSP00000355328.2	O94910-2
	ADGRL1	ENST00000340736.10	TSL:1	c.4243G>T	p.Ala1415Ser	missense	Exon 24 of 24	ENSP00000340688.5	O94910-1
	ADGRL1-AS1	ENST00000588387.3	TSL:1	n.80-4097C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000850 AC: 2 AN: 235266 Hom.: 0 Cov.: 14 AF XY: 0.0000178 AC XY: 2 AN XY: 112442

African (AFR) AF: 0.00 AC: 0 AN: 6058

American (AMR) AF: 0.00 AC: 0 AN: 3214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3074

East Asian (EAS) AF: 0.00 AC: 0 AN: 4180

South Asian (SAS) AF: 0.00 AC: 0 AN: 9944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 532

European-Non Finnish (NFE) AF: 0.0000104 AC: 2 AN: 192594

Other (OTH) AF: 0.00 AC: 0 AN: 8568

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.91	T
PhyloP100		1.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.37	N
REVEL	Benign	0.12
Sift	Benign	0.56	T
Sift4G	Benign	0.80	T
Polyphen		0.48	P
Vest4		0.21
MutPred		0.45		Gain of glycosylation at A1415 (P = 1e-04)
MVP		0.082
MPC		0.51
ClinPred		0.25	T
GERP RS		3.9
Varity_R		0.063
gMVP		0.31
Mutation Taster		=96/4	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: rs1268470454; hg19: chr19-14261867;