12-131040508-C-T

Variant names:

• chr12-131040508-C-T
• rs3847687
• NM_198827.5:c.1473+26168C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000261654.10(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 ENST00000261654.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261654.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRD1	NM_198827.5	MANE Select	c.1473+26168C>T		intron	N/A	NP_942122.2
	ADGRD1	NM_001330497.2		c.1569+26168C>T		intron	N/A	NP_001317426.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRD1	ENST00000261654.10	TSL:1 MANE Select	c.1473+26168C>T		intron	N/A	ENSP00000261654.5
	ADGRD1	ENST00000535015.5	TSL:1	c.1569+26168C>T		intron	N/A	ENSP00000444425.1
	ADGRD1	ENST00000376682.8	TSL:2	n.786+26168C>T		intron	N/A

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

African (AFR) AF: 0.163 AC: 6773 AN: 41532

American (AMR) AF: 0.434 AC: 6631 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1500 AN: 3472

East Asian (EAS) AF: 0.181 AC: 940 AN: 5188

South Asian (SAS) AF: 0.534 AC: 2574 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4004 AN: 10536

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30678 AN: 67982

Other (OTH) AF: 0.367 AC: 776 AN: 2114

Alfa AF: 0.408 Hom.: 34777

Bravo AF: 0.343

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.68
DANN	Benign	0.51
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3847687; hg19: chr12-131525053;