19-6904137-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001974.5(ADGRE1):c.904C>A(p.Pro302Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRE1 NM_001974.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.76

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]

LOC105372256 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20871273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRE1	NM_001974.5	c.904C>A	p.Pro302Thr	missense_variant	8/21	ENST00000312053.9
LOC105372256	XR_936288.4	n.168-2079G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRE1	ENST00000312053.9	c.904C>A	p.Pro302Thr	missense_variant	8/21	1	NM_001974.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.904C>A (p.P302T) alteration is located in exon 8 (coding exon 8) of the ADGRE1 gene. This alteration results from a C to A substitution at nucleotide position 904, causing the proline (P) at amino acid position 302 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	Benign	0.11
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	20
Dann	Benign	0.90
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Uncertain	-0.27	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.0	D;D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.024	D;T;D;D
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.87	P;.;P;.
Vest4		0.31
MutPred		0.58		Loss of disorder (P = 0.0707);.;Loss of disorder (P = 0.0707);.;
MVP		0.49
MPC		0.52
ClinPred		0.14	T
GERP RS		1.3
Varity_R		0.12
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-6904148; COSMIC: COSV51678768; COSMIC: COSV51678768;