rs1569019

Positions:

• chr12-131091646-C-A
• chr12-131091646-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198827.5(ADGRD1):​c.1671+6983C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 152,242 control chromosomes in the GnomAD database, including 659 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 0.081 (659 hom., cov: 33)
• Consequence: ADGRD1 NM_198827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.22).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRD1	NM_198827.5	c.1671+6983C>A		intron_variant		ENST00000261654.10	NP_942122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRD1	ENST00000261654.10	c.1671+6983C>A		intron_variant		1	NM_198827.5	ENSP00000261654.5

Frequencies

GnomAD3 genomes AF: 0.0815 AC: 12403 AN: 152122 Hom.: 658 Cov.: 33

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0880

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0815 AC: 12407 AN: 152242 Hom.: 659 Cov.: 33 AF XY: 0.0822 AC XY: 6116 AN XY: 74428

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.0815

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.104 Hom.: 1261

Bravo AF: 0.0738

Asia WGS AF: 0.0390 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	2.3
DANN	Benign	0.68

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: rs1569019; hg19: chr12-131576191;