19-6906458-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001974.5(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 NM_001974.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.21

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 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 GnomAd at 8 AR gene

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRE1	ENST00000312053.9	c.975T>C	p.Asp325=	synonymous_variant	9/21	1	NM_001974.5	P1

Frequencies

GnomAD3 genomes AF: 0.00662 AC: 1007 AN: 152216 Hom.: 8 Cov.: 32

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.: 6 AF XY: 0.00632 AC XY: 859 AN XY: 135816

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.: 64 Cov.: 30 AF XY: 0.00897 AC XY: 6524 AN XY: 727082

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.: 8 Cov.: 32 AF XY: 0.00611 AC XY: 455 AN XY: 74506

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.: 4

Bravo AF: 0.00662

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00956

EpiControl AF: 0.00872

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 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

Other links and lift over

dbSNP: rs78491083; hg19: chr19-6906469; COSMIC: COSV99165142; COSMIC: COSV99165142;