4-61200894-T-C

Position:

• chr4-61200894-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047416555.1(LOC124900173):​c.841T>C​(p.Phe281Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 152,028 control chromosomes in the GnomAD database, including 75,327 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 1.0 (75327 hom., cov: 31)
• Consequence: LOC124900173 XM_047416555.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

Genes affected

LOC124900173 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124900173	XM_047416555.1	c.841T>C	p.Phe281Leu	missense_variant	2/3		XP_047272511.1
ADGRL3	NM_001387552.1	c.-1111T>C		5_prime_UTR_variant	1/27	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.-1111T>C		5_prime_UTR_variant	1/27		NM_001387552.1	ENSP00000507980

Frequencies

GnomAD3 genomes AF: 0.995 AC: 151225 AN: 151918 Hom.: 75273 Cov.: 31

Gnomad AFR AF: 0.985

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.998

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.998

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.996

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

GnomAD4 genome AF: 0.995 AC: 151334 AN: 152028 Hom.: 75327 Cov.: 31 AF XY: 0.996 AC XY: 73957 AN XY: 74280

Gnomad4 AFR AF: 0.985

Gnomad4 AMR AF: 0.998

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.996

Alfa AF: 0.999 Hom.: 3326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs905963; hg19: chr4-62066612;