12-131040508-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.1473+26168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,144 control chromosomes in the GnomAD database, including 11,114 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 0.36 (11114 hom., cov: 33)
• Consequence: ADGRD1 NM_198827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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=-1.24).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRD1	NM_198827.5	c.1473+26168C>T		intron_variant		ENST00000261654.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRD1	ENST00000261654.10	c.1473+26168C>T		intron_variant		1	NM_198827.5	P4
ADGRD1	ENST00000535015.5	c.1569+26168C>T		intron_variant		1		A1
ADGRD1	ENST00000376682.8	n.786+26168C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54198 AN: 152026 Hom.: 11109 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.356 AC: 54220 AN: 152144 Hom.: 11114 Cov.: 33 AF XY: 0.357 AC XY: 26560 AN XY: 74354

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.367

Alfa AF: 0.410 Hom.: 9934

Bravo AF: 0.343

Asia WGS AF: 0.355 AC: 1232 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	0.68
Dann	Benign	0.51

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: rs3847687; hg19: chr12-131525053;