rs1968111894

Variant names:

• chr19-14151030-T-A
• rs1968111894
• NM_014921.5:c.4253A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_014921.5(ADGRL1):​c.4253A>T​(p.Tyr1418Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000016 in 1,497,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000081 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ADGRL1 NM_014921.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74
• 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29660812).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

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.4253A>T	p.Tyr1418Phe	missense	Exon 23 of 23	NP_055736.2
	ADGRL1	NM_001008701.3		c.4268A>T	p.Tyr1423Phe	missense	Exon 24 of 24	NP_001008701.1	O94910-1
	ADGRL1-AS1	NR_045214.1		n.73-4122T>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.4253A>T	p.Tyr1418Phe	missense	Exon 23 of 23	ENSP00000355328.2	O94910-2
	ADGRL1	ENST00000340736.10	TSL:1	c.4268A>T	p.Tyr1423Phe	missense	Exon 24 of 24	ENSP00000340688.5	O94910-1
	ADGRL1-AS1	ENST00000588387.3	TSL:1	n.80-4122T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000806 AC: 1 AN: 124016 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000241

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000167 AC: 23 AN: 1373148 Hom.: 0 Cov.: 37 AF XY: 0.0000208 AC XY: 14 AN XY: 674122

African (AFR) AF: 0.00 AC: 0 AN: 31524

American (AMR) AF: 0.00 AC: 0 AN: 33050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22798

East Asian (EAS) AF: 0.00 AC: 0 AN: 36844

South Asian (SAS) AF: 0.0000262 AC: 2 AN: 76262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.0000197 AC: 21 AN: 1065124

Other (OTH) AF: 0.00 AC: 0 AN: 56504

GnomAD4 genome AF: 0.00000806 AC: 1 AN: 124016 Hom.: 0 Cov.: 28 AF XY: 0.0000171 AC XY: 1 AN XY: 58546

African (AFR) AF: 0.00 AC: 0 AN: 31552

American (AMR) AF: 0.00 AC: 0 AN: 11118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3210

East Asian (EAS) AF: 0.00 AC: 0 AN: 4370

South Asian (SAS) AF: 0.000241 AC: 1 AN: 4150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60212

Other (OTH) AF: 0.00 AC: 0 AN: 1704

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	0.24	D
PhyloP100		5.7
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.57
Sift	Benign	0.041	D
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.40
MVP		0.29
MPC		1.0
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.26
gMVP		0.24
Mutation Taster		=75/25	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: rs1968111894; hg19: chr19-14261842;