19-14383661-A-G

Position:

• chr19-14383661-A-G

Variant summary

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

The NM_078481.4(ADGRE5):​c.22+2116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,716 control chromosomes in the GnomAD database, including 6,802 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 0.29 (6802 hom., cov: 29)
• Consequence: ADGRE5 NM_078481.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

Genes affected

ADGRE5 (HGNC:1711): (adhesion G protein-coupled receptor E5) This gene encodes a member of the EGF-TM7 subfamily of adhesion G protein-coupled receptors, which mediate cell-cell interactions. These proteins are cleaved by self-catalytic proteolysis into a large extracellular subunit and seven-span transmembrane subunit, which associate at the cell surface as a receptor complex. The encoded protein may play a role in cell adhesion as well as leukocyte recruitment, activation and migration, and contains multiple extracellular EGF-like repeats which mediate binding to chondroitin sulfate and the cell surface complement regulatory protein CD55. Expression of this gene may play a role in the progression of several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms with 3 to 5 EGF-like repeats have been observed for this gene. This gene is found in a cluster with other EGF-TM7 genes on the short arm of chromosome 19. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRE5	NM_078481.4	c.22+2116A>G		intron_variant		ENST00000242786.6	NP_510966.1
ADGRE5	NM_001025160.3	c.22+2116A>G		intron_variant			NP_001020331.1
ADGRE5	NM_001784.6	c.22+2116A>G		intron_variant			NP_001775.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRE5	ENST00000242786.6	c.22+2116A>G		intron_variant		1	NM_078481.4	ENSP00000242786	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43259 AN: 151598 Hom.: 6789 Cov.: 29

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.285 AC: 43299 AN: 151716 Hom.: 6802 Cov.: 29 AF XY: 0.286 AC XY: 21171 AN XY: 74146

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.310

Alfa AF: 0.316 Hom.: 15654

Bravo AF: 0.286

Asia WGS AF: 0.490 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.8
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs9917042; hg19: chr19-14494473;