chr4-61467630-A-G

Variant names:

• chr4-61467630-A-G
• rs335336
• NM_001387552.1:c.-173-29491A>G

Variant summary

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

The NM_001387552.1(ADGRL3):​c.-173-29491A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,082 control chromosomes in the GnomAD database, including 58,121 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 0.86 (58121 hom., cov: 31)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.-173-29491A>G		intron_variant	Intron 2 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-173-29491A>G		intron_variant	Intron 2 of 26		NM_001387552.1	ENSP00000507980.1
ADGRL3	ENST00000512091.6	c.-173-29491A>G		intron_variant	Intron 2 of 25	1		ENSP00000423388.1
ADGRL3	ENST00000514591.5	c.-173-29491A>G		intron_variant	Intron 2 of 24	5		ENSP00000422533.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131077 AN: 151966 Hom.: 58107 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.862 AC: 131134 AN: 152082 Hom.: 58121 Cov.: 31 AF XY: 0.865 AC XY: 64320 AN XY: 74348

African (AFR) AF: 0.629 AC: 26078 AN: 41432

American (AMR) AF: 0.925 AC: 14124 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3325 AN: 3472

East Asian (EAS) AF: 0.944 AC: 4873 AN: 5164

South Asian (SAS) AF: 0.945 AC: 4557 AN: 4820

European-Finnish (FIN) AF: 0.938 AC: 9961 AN: 10614

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65158 AN: 67990

Other (OTH) AF: 0.891 AC: 1881 AN: 2112

Alfa AF: 0.937 Hom.: 74864

Bravo AF: 0.851

Asia WGS AF: 0.925 AC: 3215 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.038
DANN	Benign	0.45
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs335336; hg19: chr4-62333348;