chr4-62017713-C-A

Variant names:

• chr4-62017713-C-A
• rs1510920
• NM_001387552.1:c.3396-11142C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387552.1(ADGRL3):​c.3396-11142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,058 control chromosomes in the GnomAD database, including 60,479 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 0.89 (60479 hom., cov: 31)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.3396-11142C>A		intron_variant	Intron 21 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.3396-11142C>A		intron_variant	Intron 21 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134726 AN: 151940 Hom.: 60446 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.933

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.901

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.901

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.887 AC: 134816 AN: 152058 Hom.: 60479 Cov.: 31 AF XY: 0.890 AC XY: 66144 AN XY: 74322

African (AFR) AF: 0.735 AC: 30457 AN: 41446

American (AMR) AF: 0.933 AC: 14261 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3291 AN: 3472

East Asian (EAS) AF: 0.838 AC: 4308 AN: 5138

South Asian (SAS) AF: 0.949 AC: 4569 AN: 4816

European-Finnish (FIN) AF: 0.979 AC: 10370 AN: 10596

Middle Eastern (MID) AF: 0.901 AC: 263 AN: 292

European-Non Finnish (NFE) AF: 0.949 AC: 64518 AN: 67992

Other (OTH) AF: 0.902 AC: 1903 AN: 2110

Alfa AF: 0.938 Hom.: 92843

Bravo AF: 0.873

Asia WGS AF: 0.886 AC: 3080 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.21
PhyloP100		-0.071
Mutation Taster		=100/0	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: rs1510920; hg19: chr4-62883431;