19-6897184-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001974.5(ADGRE1):c.274G>C(p.Gly92Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00974 in 1,610,958 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0097 (16 hom., cov: 28)
  • Exomes 𝑓: 0.0097 (129 hom.)
• Consequence: ADGRE1 NM_001974.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.41

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062499344).
• BP6: Variant 19-6897184-G-C is Benign according to our data. Variant chr19-6897184-G-C is described in ClinVar as [Benign]. Clinvar id is 770804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRE1	NM_001974.5	c.274G>C	p.Gly92Arg	missense_variant	4/21	ENST00000312053.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRE1	ENST00000312053.9	c.274G>C	p.Gly92Arg	missense_variant	4/21	1	NM_001974.5	P1

Frequencies

GnomAD3 genomes AF: 0.00967 AC: 1444 AN: 149288 Hom.: 16 Cov.: 28

Gnomad AFR AF: 0.00160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00488

Gnomad FIN AF: 0.0460

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0114

Gnomad OTH AF: 0.00925

GnomAD3 exomes AF: 0.0104 AC: 2617 AN: 251316 Hom.: 33 AF XY: 0.0104 AC XY: 1408 AN XY: 135830

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00208

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00474

Gnomad FIN exome AF: 0.0477

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00975 AC: 14243 AN: 1461552 Hom.: 129 Cov.: 35 AF XY: 0.00961 AC XY: 6988 AN XY: 727082

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00353

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00485

Gnomad4 FIN exome AF: 0.0452

Gnomad4 NFE exome AF: 0.00955

Gnomad4 OTH exome AF: 0.00888

GnomAD4 genome AF: 0.00966 AC: 1444 AN: 149406 Hom.: 16 Cov.: 28 AF XY: 0.0108 AC XY: 789 AN XY: 72770

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00622

Gnomad4 ASJ AF: 0.00289

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00488

Gnomad4 FIN AF: 0.0460

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.00915

Alfa AF: 0.00972 Hom.: 6

Bravo AF: 0.00612

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.0101 AC: 39

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.0101 AC: 87

ExAC AF: 0.00983 AC: 1193

EpiCase AF: 0.00894

EpiControl AF: 0.00931

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

Invitae

Apr 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.12
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	0.082
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D;D;D;D
MetaRNN	Benign	0.0062	T;T;T;T
MetaSVM	Uncertain	0.44	D
MutationTaster	Benign	0.87	D;D;D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.9	D;D;D;.
REVEL	Uncertain	0.48
Sift	Benign	0.050	D;D;D;.
Sift4G	Uncertain	0.050	T;D;T;D
Polyphen		1.0	D;D;.;.
Vest4		0.65
MPC		0.53
ClinPred		0.065	T
GERP RS		2.8
Varity_R		0.16
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs112217832; hg19: chr19-6897195; COSMIC: COSV104565857; COSMIC: COSV104565857;