Variant 19-6906458-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000312053.9(ADGRE1):c.975T>C(p.Asp325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0089 in 1,613,896 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 64 hom. )

Consequence

ADGRE1
ENST00000312053.9 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.21

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:

LOC105372256 (HGNC:):

LOC105372256 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-6906458-T-C is Benign according to our data. Variant chr19-6906458-T-C is described in ClinVar as [Benign]. Clinvar id is 3024979.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.21 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRE1	NM_001974.5 linkuse as main transcript	c.975T>C	p.Asp325=	synonymous_variant	9/21	ENST00000312053.9	NP_001965.3
LOC105372256	XR_936288.4 linkuse as main transcript	n.168-4400A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRE1	ENST00000312053.9 linkuse as main transcript	c.975T>C	p.Asp325=	synonymous_variant	9/21	1	NM_001974.5	ENSP00000311545	P1	Q14246-1

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1007

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00620

AC:

1558

AN:

251274

Hom.:

AF XY:

0.00632

AC XY:

859

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00379

Gnomad FIN exome

AF:

0.00250

Gnomad NFE exome

AF:

0.00991

Gnomad OTH exome

AF:

0.00572

GnomAD4 exome

AF:

0.00913

AC:

13351

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00897

AC XY:

6524

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.0102

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00394

Gnomad4 FIN exome

AF:

0.00243

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00855

GnomAD4 genome

AF:

0.00660

AC:

1006

AN:

152334

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00517

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00934

Hom.:

Bravo

AF:

0.00662

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00956

EpiControl

AF:

0.00872

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

ADGRE1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.1

DANN

Benign

0.39

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