Variant 19-6897482-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000312053.9(ADGRE1):c.449A>C(p.Asn150Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,446,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRE1
ENST00000312053.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

Variant links:

Genes affected

ADGRE1 (HGNC:3336): (adhesion G protein-coupled receptor E1) This gene encodes a protein that has a domain resembling seven transmembrane G protein-coupled hormone receptors (7TM receptors) at its C-terminus. The N-terminus of the encoded protein has six EGF-like modules, separated from the transmembrane segments by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ADGRE1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRE1	NM_001974.5 linkuse as main transcript	c.449A>C	p.Asn150Thr	missense_variant	5/21	ENST00000312053.9	NP_001965.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRE1	ENST00000312053.9 linkuse as main transcript	c.449A>C	p.Asn150Thr	missense_variant	5/21	1	NM_001974.5	ENSP00000311545	P1	Q14246-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000423

AC:

AN:

236474

Hom.:

AF XY:

0.00000781

AC XY:

AN XY:

128016

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000570

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1446144

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.449A>C (p.N150T) alteration is located in exon 5 (coding exon 5) of the ADGRE1 gene. This alteration results from a A to C substitution at nucleotide position 449, causing the asparagine (N) at amino acid position 150 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.58

.;D;.;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.94

D;D;D;D

MetaSVM

Pathogenic

0.89

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.7

D;D;D;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.0020

D;D;D;.

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.38

MutPred

0.92

Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);.;.;

MVP

0.79

MPC

0.50

ClinPred

0.59

GERP RS

2.0

Varity_R

0.82

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over