Genetic Variant ADGRE1:c.31+86G>A (chr19-6887725-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001974.5(ADGRE1):c.31+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 1,429,386 control chromosomes in the GnomAD database, including 8,009 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.090 ( 955 hom., cov: 31)

Exomes 𝑓: 0.094 ( 7054 hom. )

Consequence

ADGRE1
NM_001974.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001974.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADGRE1	NM_001974.5	MANE Select	c.31+86G>A	intron	N/A	NP_001965.3
ADGRE1	NM_001256252.2		c.31+86G>A	intron	N/A	NP_001243181.1
ADGRE1	NM_001256253.2		c.31+86G>A	intron	N/A	NP_001243182.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADGRE1	ENST00000312053.9	TSL:1 MANE Select	c.31+86G>A	intron	N/A	ENSP00000311545.3
ADGRE1	ENST00000250572.12	TSL:1	c.31+86G>A	intron	N/A	ENSP00000250572.7
ADGRE1	ENST00000381404.8	TSL:2	c.31+86G>A	intron	N/A	ENSP00000370811.4

Frequencies

GnomAD3 genomes

AF:

0.0896

AC:

13633

AN:

152088

Hom.:

958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.0952

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0881

Gnomad OTH

AF:

0.0990

GnomAD4 exome

AF:

0.0944

AC:

120619

AN:

1277180

Hom.:

7054

AF XY:

0.0943

AC XY:

60348

AN XY:

639816

show subpopulations

African (AFR)

AF:

0.0226

AC:

617

AN:

27324

American (AMR)

AF:

0.184

AC:

5542

AN:

30140

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

2586

AN:

22632

East Asian (EAS)

AF:

0.282

AC:

10383

AN:

36792

South Asian (SAS)

AF:

0.0779

AC:

5790

AN:

74280

European-Finnish (FIN)

AF:

0.151

AC:

7935

AN:

52392

Middle Eastern (MID)

AF:

0.133

AC:

634

AN:

4772

European-Non Finnish (NFE)

AF:

0.0838

AC:

81761

AN:

975154

Other (OTH)

AF:

0.100

AC:

5371

AN:

53694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5189

10378

15568

20757

25946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2948

5896

8844

11792

14740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0896

AC:

13633

AN:

152206

Hom.:

955

Cov.:

AF XY:

0.0954

AC XY:

7096

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0243

AC:

1009

AN:

41550

American (AMR)

AF:

0.138

AC:

2116

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

351

AN:

3470

East Asian (EAS)

AF:

0.304

AC:

1571

AN:

5168

South Asian (SAS)

AF:

0.0953

AC:

459

AN:

4818

European-Finnish (FIN)

AF:

0.163

AC:

1725

AN:

10596

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0881

AC:

5989

AN:

68004

Other (OTH)

AF:

0.0975

AC:

206

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

600

1201

1801

2402

3002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0882

Hom.:

1227

Bravo

AF:

0.0882

Asia WGS

AF:

0.169

AC:

589

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.5

(source)

DANN

Benign

0.58

PhyloP100

1.2

PromoterAI

-0.0050

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over