4-61351277-T-A

Variant names:

• chr4-61351277-T-A
• rs4860091
• NM_001387552.1:c.-239-31847T>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.-239-31847T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,998 control chromosomes in the GnomAD database, including 19,899 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 0.48 (19899 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.-239-31847T>A		intron_variant	Intron 1 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-239-31847T>A		intron_variant	Intron 1 of 26		NM_001387552.1	ENSP00000507980.1
ADGRL3	ENST00000512091.6	c.-239-31847T>A		intron_variant	Intron 1 of 25	1		ENSP00000423388.1
ADGRL3	ENST00000514591.5	c.-239-31847T>A		intron_variant	Intron 1 of 24	5		ENSP00000422533.1
ADGRL3	ENST00000509779.5	n.103-31847T>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73273 AN: 151878 Hom.: 19894 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.482 AC: 73286 AN: 151998 Hom.: 19899 Cov.: 32 AF XY: 0.482 AC XY: 35788 AN XY: 74280

African (AFR) AF: 0.224 AC: 9279 AN: 41484

American (AMR) AF: 0.553 AC: 8445 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2053 AN: 3468

East Asian (EAS) AF: 0.684 AC: 3515 AN: 5138

South Asian (SAS) AF: 0.380 AC: 1834 AN: 4822

European-Finnish (FIN) AF: 0.555 AC: 5853 AN: 10554

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40450 AN: 67942

Other (OTH) AF: 0.508 AC: 1070 AN: 2108

Alfa AF: 0.523 Hom.: 2700

Bravo AF: 0.476

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		0.45
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: rs4860091; hg19: chr4-62216995;