12-130971904-G-A

Position:

• chr12-130971904-G-A

Variant summary

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

The NM_198827.5(ADGRD1):​c.310+324G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0728 in 152,230 control chromosomes in the GnomAD database, including 775 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 0.073 (775 hom., cov: 32)
• Consequence: ADGRD1 NM_198827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRD1	NM_198827.5	c.310+324G>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.310+324G>A		intron_variant		1	NM_198827.5	ENSP00000261654	P4

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11022 AN: 152114 Hom.: 759 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0455

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0508

Gnomad SAS AF: 0.0616

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0728 AC: 11081 AN: 152230 Hom.: 775 Cov.: 32 AF XY: 0.0728 AC XY: 5416 AN XY: 74446

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.0509

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0345 Hom.: 216

Bravo AF: 0.0781

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.046
DANN	Benign	0.63

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: rs11061269; hg19: chr12-131456449;