19-14397914-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_078481.4(ADGRE5):c.798G>A(p.Pro266=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000043 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRE5 NM_078481.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.376

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-14397914-G-A is Benign according to our data. Variant chr19-14397914-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649420.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.376 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRE5	NM_078481.4	c.798G>A	p.Pro266=	synonymous_variant	8/20	ENST00000242786.6
ADGRE5	NM_001025160.3	c.651G>A	p.Pro217=	synonymous_variant	7/19
ADGRE5	NM_001784.6	c.519G>A	p.Pro173=	synonymous_variant	6/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRE5	ENST00000242786.6	c.798G>A	p.Pro266=	synonymous_variant	8/20	1	NM_078481.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000429 AC: 5 AN: 116446 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.0000349

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000290

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000175

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000366 AC: 6 AN: 163716 Hom.: 0 AF XY: 0.0000449 AC XY: 4 AN XY: 89016

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.000230

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000435 AC: 52 AN: 1195086 Hom.: 0 Cov.: 23 AF XY: 0.0000452 AC XY: 27 AN XY: 597060

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000288

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000282

Gnomad4 SAS exome AF: 0.0000274

Gnomad4 FIN exome AF: 0.0000215

Gnomad4 NFE exome AF: 0.0000411

Gnomad4 OTH exome AF: 0.000118

GnomAD4 genome AF: 0.0000429 AC: 5 AN: 116536 Hom.: 0 Cov.: 17 AF XY: 0.0000363 AC XY: 2 AN XY: 55050

Gnomad4 AFR AF: 0.0000348

Gnomad4 AMR AF: 0.000289

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000175

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000480 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

ADGRE5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.0
Dann	Benign	0.54

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: rs752522386; hg19: chr19-14508726; COSMIC: COSV99662888; COSMIC: COSV99662888;