rs6551640

Variant names:

• chr4-61653103-T-A
• rs6551640
• NM_001387552.1:c.474-23723T>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.474-23723T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,204 control chromosomes in the GnomAD database, including 11,657 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 0.37 (11657 hom., cov: 29)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.474-23723T>A		intron_variant	Intron 5 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.474-23723T>A		intron_variant	Intron 5 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55380 AN: 151082 Hom.: 11659 Cov.: 29

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.480

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.366 AC: 55374 AN: 151204 Hom.: 11657 Cov.: 29 AF XY: 0.359 AC XY: 26501 AN XY: 73772

African (AFR) AF: 0.184 AC: 7556 AN: 41170

American (AMR) AF: 0.351 AC: 5331 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1625 AN: 3464

East Asian (EAS) AF: 0.0775 AC: 396 AN: 5112

South Asian (SAS) AF: 0.394 AC: 1875 AN: 4762

European-Finnish (FIN) AF: 0.363 AC: 3768 AN: 10378

Middle Eastern (MID) AF: 0.483 AC: 138 AN: 286

European-Non Finnish (NFE) AF: 0.493 AC: 33467 AN: 67836

Other (OTH) AF: 0.393 AC: 827 AN: 2106

Alfa AF: 0.425 Hom.: 1790

Bravo AF: 0.353

Asia WGS AF: 0.217 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		0.24
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: rs6551640; hg19: chr4-62518821;