Genetic Variant ADGRD1:c.2436+203A>G (chr12-131137217-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_198827.5(ADGRD1):c.2436+203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 610,648 control chromosomes in the GnomAD database, including 124,772 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 0.64 ( 31127 hom., cov: 34)

Exomes 𝑓: 0.63 ( 93645 hom. )

Consequence

ADGRD1
NM_198827.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.29

Publications

30 publications found

Variant links:

Genes affected

ADGRD1 (HGNC:19893): (adhesion G protein-coupled receptor D1) The adhesion G-protein-coupled receptors (GPCRs), including GPR133, are membrane-bound proteins with long N termini containing multiple domains. GPCRs, or GPRs, contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins (summary by Bjarnadottir et al., 2004 [PubMed 15203201]).[supplied by OMIM, Nov 2010]

ADGRD1 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=-1.25).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198827.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRD1	NM_198827.5	MANE Select	c.2436+203A>G		intron	N/A	NP_942122.2
	ADGRD1	NM_001330497.2		c.2532+203A>G		intron	N/A	NP_001317426.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADGRD1	ENST00000261654.10	TSL:1 MANE Select	c.2436+203A>G	intron	N/A	ENSP00000261654.5
ADGRD1	ENST00000535015.5	TSL:1	c.2532+203A>G	intron	N/A	ENSP00000444425.1
ADGRD1	ENST00000543617.2	TSL:1	c.993+203A>G	intron	N/A	ENSP00000438021.1

Frequencies

GnomAD3 genomes

AF:

0.636

AC:

96589

AN:

151962

Hom.:

31080

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.671

Gnomad OTH

AF:

0.644

GnomAD4 exome

AF:

0.635

AC:

291070

AN:

458570

Hom.:

93645

AF XY:

0.638

AC XY:

155532

AN XY:

243960

show subpopulations

African (AFR)

AF:

0.662

AC:

8380

AN:

12666

American (AMR)

AF:

0.434

AC:

9075

AN:

20896

Ashkenazi Jewish (ASJ)

AF:

0.698

AC:

9772

AN:

14010

East Asian (EAS)

AF:

0.441

AC:

13655

AN:

30950

South Asian (SAS)

AF:

0.632

AC:

29623

AN:

46852

European-Finnish (FIN)

AF:

0.603

AC:

18073

AN:

29988

Middle Eastern (MID)

AF:

0.726

AC:

1450

AN:

1996

European-Non Finnish (NFE)

AF:

0.669

AC:

183995

AN:

274900

Other (OTH)

AF:

0.648

AC:

17047

AN:

26312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5140

10280

15421

20561

25701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.636

AC:

96689

AN:

152078

Hom.:

31127

Cov.:

AF XY:

0.627

AC XY:

46621

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.663

AC:

27535

AN:

41508

American (AMR)

AF:

0.512

AC:

7815

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

2412

AN:

3470

East Asian (EAS)

AF:

0.440

AC:

2263

AN:

5146

South Asian (SAS)

AF:

0.632

AC:

3050

AN:

4826

European-Finnish (FIN)

AF:

0.568

AC:

5992

AN:

10558

Middle Eastern (MID)

AF:

0.747

AC:

218

AN:

292

European-Non Finnish (NFE)

AF:

0.671

AC:

45591

AN:

67984

Other (OTH)

AF:

0.646

AC:

1362

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1829

3657

5486

7314

9143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.653

Hom.:

79657

Bravo

AF:

0.625

Asia WGS

AF:

0.556

AC:

1933

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.3

CADD

Benign

0.43

(source)

DANN

Benign

0.45

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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