19-14641513-C-T

Variant names:

• chr19-14641513-C-T
• rs45508602
• NM_032571.5:c.1154G>A

Variant summary

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

The NM_032571.5(ADGRE3):​c.1154G>A​(p.Arg385Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,613,850 control chromosomes in the GnomAD database, including 598,279 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.83 (53340 hom., cov: 31)
  • Exomes 𝑓: 0.86 (544939 hom.)
• Consequence: ADGRE3 NM_032571.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 19 publications found

Genes affected

ADGRE3 (HGNC:23647): (adhesion G protein-coupled receptor E3) This gene encodes a member of the class B seven-span transmembrane (TM7) receptor family expressed predominantly by cells of the immune system. Family members are characterized by an extended extracellular region with a variable number of N-terminal epidermal growth factor (EGF)-like domains coupled to a TM7 domain via a mucin-like spacer domain. This gene is closely linked to the gene encoding egf-like molecule containing mucin-like hormone receptor 2 on chromosome 19. This protein may play a role in myeloid-myeloid interactions during immune and inflammatory responses. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.2887201E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032571.5. 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
	ADGRE3	NM_032571.5	MANE Select	c.1154G>A	p.Arg385Gln	missense	Exon 10 of 16	NP_115960.2	Q9BY15-1
	ADGRE3	NM_001289158.2		c.998G>A	p.Arg333Gln	missense	Exon 9 of 15	NP_001276087.1	Q9BY15-2
	ADGRE3	NM_001289159.2		c.776G>A	p.Arg259Gln	missense	Exon 7 of 13	NP_001276088.1	E7EW83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRE3	ENST00000253673.6	TSL:1 MANE Select	c.1154G>A	p.Arg385Gln	missense	Exon 10 of 16	ENSP00000253673.4	Q9BY15-1
	ADGRE3	ENST00000344373.8	TSL:1	c.998G>A	p.Arg333Gln	missense	Exon 9 of 15	ENSP00000340758.4	Q9BY15-2
	ADGRE3	ENST00000718247.1		c.1154G>A	p.Arg385Gln	missense	Exon 10 of 16	ENSP00000520692.1	A0ABB0MV84

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126945 AN: 152018 Hom.: 53309 Cov.: 31

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.847

GnomAD2 exomes AF: 0.869 AC: 218261 AN: 251064 AF XY: 0.874

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.932

Gnomad ASJ exome AF: 0.856

Gnomad EAS exome AF: 0.868

Gnomad FIN exome AF: 0.850

Gnomad NFE exome AF: 0.852

Gnomad OTH exome AF: 0.874

GnomAD4 exome AF: 0.863 AC: 1261354 AN: 1461714 Hom.: 544939 Cov.: 75 AF XY: 0.865 AC XY: 629269 AN XY: 727160

African (AFR) AF: 0.745 AC: 24946 AN: 33468

American (AMR) AF: 0.928 AC: 41492 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 22225 AN: 26134

East Asian (EAS) AF: 0.859 AC: 34089 AN: 39698

South Asian (SAS) AF: 0.945 AC: 81479 AN: 86256

European-Finnish (FIN) AF: 0.849 AC: 45349 AN: 53414

Middle Eastern (MID) AF: 0.890 AC: 5131 AN: 5768

European-Non Finnish (NFE) AF: 0.859 AC: 954575 AN: 1111870

Other (OTH) AF: 0.862 AC: 52068 AN: 60388

GnomAD4 genome AF: 0.835 AC: 127026 AN: 152136 Hom.: 53340 Cov.: 31 AF XY: 0.837 AC XY: 62263 AN XY: 74378

African (AFR) AF: 0.748 AC: 31021 AN: 41454

American (AMR) AF: 0.905 AC: 13840 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2932 AN: 3468

East Asian (EAS) AF: 0.859 AC: 4443 AN: 5174

South Asian (SAS) AF: 0.951 AC: 4588 AN: 4822

European-Finnish (FIN) AF: 0.845 AC: 8964 AN: 10604

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58388 AN: 68010

Other (OTH) AF: 0.844 AC: 1780 AN: 2108

Alfa AF: 0.860 Hom.: 60587

Bravo AF: 0.835

ESP6500AA AF: 0.756 AC: 3332

ESP6500EA AF: 0.857 AC: 7368

ExAC AF: 0.864 AC: 104909

Asia WGS AF: 0.891 AC: 3099 AN: 3478

EpiCase AF: 0.858

EpiControl AF: 0.849

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.36
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-0.98	T
PhyloP100		2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	3.4	N
REVEL	Benign	0.082
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0050	B
Vest4		0.074
MPC		0.16
ClinPred		0.0052	T
GERP RS		2.8
Varity_R		0.037
gMVP		0.20
Mutation Taster		=99/1	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: rs45508602; hg19: chr19-14752325; COSMIC: COSV53730932;