4-61935010-T-C

Variant names:

• chr4-61935010-T-C
• rs734644
• NM_001387552.1:c.2283T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001387552.1(ADGRL3):​c.2283T>C​(p.Asn761Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 1,612,898 control chromosomes in the GnomAD database, including 437,210 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 0.74 (41749 hom., cov: 32)
  • Exomes 𝑓: 0.73 (395461 hom.)
• Consequence: ADGRL3 NM_001387552.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 34 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.155).
• BP7: Synonymous conserved (PhyloP=1.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387552.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	NM_001387552.1	MANE Select	c.2283T>C	p.Asn761Asn	synonymous	Exon 14 of 27	NP_001374481.1	A0A804HKL8
	ADGRL3	NM_001322402.3		c.2283T>C	p.Asn761Asn	synonymous	Exon 14 of 26	NP_001309331.1
	ADGRL3	NM_001371344.2		c.2283T>C	p.Asn761Asn	synonymous	Exon 13 of 24	NP_001358273.1	E7EVD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRL3	ENST00000683033.1	MANE Select	c.2283T>C	p.Asn761Asn	synonymous	Exon 14 of 27	ENSP00000507980.1	A0A804HKL8
	ADGRL3	ENST00000512091.6	TSL:1	c.2079T>C	p.Asn693Asn	synonymous	Exon 13 of 26	ENSP00000423388.1	Q9HAR2-2
	ADGRL3	ENST00000506720.5	TSL:5	c.2283T>C	p.Asn761Asn	synonymous	Exon 12 of 25	ENSP00000420931.1	E7EUW2

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112049 AN: 151890 Hom.: 41715 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.727

GnomAD2 exomes AF: 0.695 AC: 172771 AN: 248604 AF XY: 0.693

Gnomad AFR exome AF: 0.797

Gnomad AMR exome AF: 0.567

Gnomad ASJ exome AF: 0.681

Gnomad EAS exome AF: 0.607

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.712

GnomAD4 exome AF: 0.734 AC: 1071799 AN: 1460890 Hom.: 395461 Cov.: 44 AF XY: 0.730 AC XY: 530718 AN XY: 726720

African (AFR) AF: 0.793 AC: 26532 AN: 33446

American (AMR) AF: 0.579 AC: 25871 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 17844 AN: 26116

East Asian (EAS) AF: 0.591 AC: 23459 AN: 39686

South Asian (SAS) AF: 0.637 AC: 54919 AN: 86230

European-Finnish (FIN) AF: 0.750 AC: 40015 AN: 53380

Middle Eastern (MID) AF: 0.692 AC: 3986 AN: 5760

European-Non Finnish (NFE) AF: 0.751 AC: 835058 AN: 1111286

Other (OTH) AF: 0.731 AC: 44115 AN: 60342

GnomAD4 genome AF: 0.738 AC: 112143 AN: 152008 Hom.: 41749 Cov.: 32 AF XY: 0.730 AC XY: 54231 AN XY: 74290

African (AFR) AF: 0.797 AC: 33031 AN: 41454

American (AMR) AF: 0.646 AC: 9875 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2379 AN: 3464

East Asian (EAS) AF: 0.600 AC: 3085 AN: 5138

South Asian (SAS) AF: 0.627 AC: 3013 AN: 4808

European-Finnish (FIN) AF: 0.737 AC: 7795 AN: 10572

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50721 AN: 67974

Other (OTH) AF: 0.728 AC: 1540 AN: 2114

Alfa AF: 0.736 Hom.: 87281

Bravo AF: 0.732

Asia WGS AF: 0.630 AC: 2192 AN: 3478

EpiCase AF: 0.743

EpiControl AF: 0.743

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	6.9
DANN	Benign	0.72
PhyloP100		1.8
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: rs734644; hg19: chr4-62800728; COSMIC: COSV72231149;