chr12-131137217-A-G

Variant names:

• chr12-131137217-A-G
• rs885389
• NM_198827.5:c.2436+203A>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.2436+203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 610,648 control chromosomes in the GnomAD database, including 124,772 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 0.64 (31127 hom., cov: 34)
  • Exomes 𝑓: 0.63 (93645 hom.)
• Consequence: ADGRD1 NM_198827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 30 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=-1.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRD1	NM_198827.5	c.2436+203A>G		intron_variant	Intron 23 of 24	ENST00000261654.10	NP_942122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRD1	ENST00000261654.10	c.2436+203A>G		intron_variant	Intron 23 of 24	1	NM_198827.5	ENSP00000261654.5

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96589 AN: 151962 Hom.: 31080 Cov.: 34

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.635 AC: 291070 AN: 458570 Hom.: 93645 AF XY: 0.638 AC XY: 155532 AN XY: 243960

African (AFR) AF: 0.662 AC: 8380 AN: 12666

American (AMR) AF: 0.434 AC: 9075 AN: 20896

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 9772 AN: 14010

East Asian (EAS) AF: 0.441 AC: 13655 AN: 30950

South Asian (SAS) AF: 0.632 AC: 29623 AN: 46852

European-Finnish (FIN) AF: 0.603 AC: 18073 AN: 29988

Middle Eastern (MID) AF: 0.726 AC: 1450 AN: 1996

European-Non Finnish (NFE) AF: 0.669 AC: 183995 AN: 274900

Other (OTH) AF: 0.648 AC: 17047 AN: 26312

GnomAD4 genome AF: 0.636 AC: 96689 AN: 152078 Hom.: 31127 Cov.: 34 AF XY: 0.627 AC XY: 46621 AN XY: 74330

African (AFR) AF: 0.663 AC: 27535 AN: 41508

American (AMR) AF: 0.512 AC: 7815 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2412 AN: 3470

East Asian (EAS) AF: 0.440 AC: 2263 AN: 5146

South Asian (SAS) AF: 0.632 AC: 3050 AN: 4826

European-Finnish (FIN) AF: 0.568 AC: 5992 AN: 10558

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.671 AC: 45591 AN: 67984

Other (OTH) AF: 0.646 AC: 1362 AN: 2108

Alfa AF: 0.653 Hom.: 79657

Bravo AF: 0.625

Asia WGS AF: 0.556 AC: 1933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.3
CADD	Benign	0.43
DANN	Benign	0.45
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs885389; hg19: chr12-131621762; COSMIC: COSV55461720; COSMIC: COSV55461720;