4-61201293-A-T

Variant names:

• chr4-61201293-A-T
• rs1505666
• NM_001387552.1:c.-712A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387552.1(ADGRL3):​c.-712A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRL3 NM_001387552.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• 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]

LOC124900173 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.-712A>T		5_prime_UTR_variant	Exon 1 of 27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-712A>T		5_prime_UTR_variant	Exon 1 of 27		NM_001387552.1	ENSP00000507980.1
ADGRL3	ENST00000512091.6	c.-712A>T		5_prime_UTR_variant	Exon 1 of 26	1		ENSP00000423388.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1650 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1104

African (AFR) AF: 0.00 AC: 0 AN: 26

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 36

South Asian (SAS) AF: 0.00 AC: 0 AN: 376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 18

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 730

Other (OTH) AF: 0.00 AC: 0 AN: 20

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.9
DANN	Benign	0.64
PhyloP100		-0.28
PromoterAI		-0.069	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1505666; hg19: chr4-62067011;