Genetic Variant ADGRD1:c.-83C>T (chr12-131084560-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000335486.10(ADGRD1):c.-83C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0272 in 1,614,052 control chromosomes in the GnomAD database, including 748 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 0.022 ( 43 hom., cov: 32)

Exomes 𝑓: 0.028 ( 705 hom. )

Consequence

ADGRD1
ENST00000335486.10 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.66

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007883668).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3305/152278) while in subpopulation NFE AF= 0.0304 (2067/68018). AF 95% confidence interval is 0.0293. There are 43 homozygotes in gnomad4. There are 1643 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRD1	NM_198827.5 link	c.1568C>T	p.Ser523Leu	missense_variant	Exon 15 of 25	ENST00000261654.10	NP_942122.2	Q6QNK2-1Q9NSM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRD1	ENST00000261654.10 link	c.1568C>T	p.Ser523Leu	missense_variant	Exon 15 of 25	1	NM_198827.5	ENSP00000261654.5		Q6QNK2-1

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3304

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00512

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0262

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.000965

Gnomad SAS

AF:

0.0273

Gnomad FIN

AF:

0.0334

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0304

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.0249

AC:

6269

AN:

251326

Hom.:

112

AF XY:

0.0254

AC XY:

3451

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00492

Gnomad AMR exome

AF:

0.0228

Gnomad ASJ exome

AF:

0.0208

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0227

Gnomad FIN exome

AF:

0.0364

Gnomad NFE exome

AF:

0.0315

Gnomad OTH exome

AF:

0.0206

GnomAD4 exome

AF:

0.0278

AC:

40580

AN:

1461774

Hom.:

705

Cov.:

AF XY:

0.0278

AC XY:

20193

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00460

Gnomad4 AMR exome

AF:

0.0253

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0229

Gnomad4 FIN exome

AF:

0.0367

Gnomad4 NFE exome

AF:

0.0300

Gnomad4 OTH exome

AF:

0.0245

GnomAD4 genome

AF:

0.0217

AC:

3305

AN:

152278

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1643

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0245

Gnomad4 EAS

AF:

0.000967

Gnomad4 SAS

AF:

0.0273

Gnomad4 FIN

AF:

0.0334

Gnomad4 NFE

AF:

0.0304

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0252

Hom.:

140

Bravo

AF:

0.0201

TwinsUK

AF:

0.0329

AC:

122

ALSPAC

AF:

0.0278

AC:

107

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0305

AC:

262

ExAC

AF:

0.0259

AC:

3141

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.59

D;.;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.62

LIST_S2

Benign

0.84

T;T;D

MetaRNN

Benign

0.0079

T;T;T

MetaSVM

Uncertain

-0.093

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.032

D;D;T

Polyphen

0.98

D;.;D

Vest4

0.84

MPC

0.62

ClinPred

0.038

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.58

gMVP

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over