12-131137217-A-C

Variant names:

• chr12-131137217-A-C
• rs885389
• NM_198827.5:c.2436+203A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198827.5(ADGRD1):​c.2436+203A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.26).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 459174 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 244278

African (AFR) AF: 0.00 AC: 0 AN: 12680

American (AMR) AF: 0.00 AC: 0 AN: 20936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14042

East Asian (EAS) AF: 0.00 AC: 0 AN: 31016

South Asian (SAS) AF: 0.00 AC: 0 AN: 46878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1998

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 275246

Other (OTH) AF: 0.00 AC: 0 AN: 26350

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 79657

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.3
CADD	Benign	0.29
DANN	Benign	0.48
PhyloP100		-2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;