4-61952750-T-C

Variant names:

• chr4-61952750-T-C
• rs995447
• NM_001387552.1:c.2805+4474T>C

Variant summary

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

The NM_001387552.1(ADGRL3):​c.2805+4474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,134 control chromosomes in the GnomAD database, including 781 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 0.091 (781 hom., cov: 32)
• Consequence: ADGRL3 NM_001387552.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRL3	NM_001387552.1	c.2805+4474T>C		intron_variant	Intron 17 of 26	ENST00000683033.1	NP_001374481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRL3	ENST00000683033.1	c.2805+4474T>C		intron_variant	Intron 17 of 26		NM_001387552.1	ENSP00000507980.1

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13890 AN: 152014 Hom.: 782 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0567

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0557

Gnomad OTH AF: 0.0798

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

GnomAD4 genome AF: 0.0914 AC: 13908 AN: 152134 Hom.: 781 Cov.: 32 AF XY: 0.0941 AC XY: 6998 AN XY: 74374

African (AFR) AF: 0.136 AC: 5648 AN: 41508

American (AMR) AF: 0.0859 AC: 1313 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0567 AC: 197 AN: 3472

East Asian (EAS) AF: 0.184 AC: 946 AN: 5142

South Asian (SAS) AF: 0.174 AC: 841 AN: 4820

European-Finnish (FIN) AF: 0.0852 AC: 902 AN: 10588

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0557 AC: 3787 AN: 68002

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.0697 Hom.: 416

Bravo AF: 0.0927

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.27
PhyloP100		0.086
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: rs995447; hg19: chr4-62818468;