chr12-131124981-A-G

Variant names:

• chr12-131124981-A-G
• rs1725789
• NM_198827.5:c.2175+4068A>G

Variant summary

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

The NM_198827.5(ADGRD1):​c.2175+4068A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,114 control chromosomes in the GnomAD database, including 2,824 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 0.17 (2824 hom., cov: 32)
• Consequence: ADGRD1 NM_198827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912
• Publications: 4 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=-1.23).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRD1	NM_198827.5	c.2175+4068A>G		intron_variant	Intron 20 of 24	ENST00000261654.10	NP_942122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRD1	ENST00000261654.10	c.2175+4068A>G		intron_variant	Intron 20 of 24	1	NM_198827.5	ENSP00000261654.5

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26597 AN: 151996 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.175 AC: 26601 AN: 152114 Hom.: 2824 Cov.: 32 AF XY: 0.170 AC XY: 12669 AN XY: 74374

African (AFR) AF: 0.0851 AC: 3533 AN: 41518

American (AMR) AF: 0.186 AC: 2847 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 818 AN: 3464

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5176

South Asian (SAS) AF: 0.0734 AC: 354 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2050 AN: 10576

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.236 AC: 16068 AN: 67972

Other (OTH) AF: 0.211 AC: 446 AN: 2116

Alfa AF: 0.218 Hom.: 10376

Bravo AF: 0.176

Asia WGS AF: 0.0670 AC: 234 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	0.56
DANN	Benign	0.65
PhyloP100		0.91
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: rs1725789; hg19: chr12-131609526; COSMIC: COSV55453004;