12-131091900-C-T

Variant names:

• chr12-131091900-C-T
• rs1976930
• NM_198827.5:c.1671+7237C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198827.5(ADGRD1):​c.1671+7237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,320 control chromosomes in the GnomAD database, including 707 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 0.090 (704 hom., cov: 33)
  • Exomes 𝑓: 0.14 (3 hom.)
• Consequence: ADGRD1 NM_198827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821

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=-1.21).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRD1	NM_198827.5	c.1671+7237C>T		intron_variant	Intron 15 of 24	ENST00000261654.10	NP_942122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRD1	ENST00000261654.10	c.1671+7237C>T		intron_variant	Intron 15 of 24	1	NM_198827.5	ENSP00000261654.5

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13641 AN: 152104 Hom.: 702 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0160

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0947

GnomAD4 exome AF: 0.143 AC: 14 AN: 98 Hom.: 3 Cov.: 0 AF XY: 0.114 AC XY: 8 AN XY: 70

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0897 AC: 13653 AN: 152222 Hom.: 704 Cov.: 33 AF XY: 0.0903 AC XY: 6721 AN XY: 74432

Gnomad4 AFR AF: 0.0498

Gnomad4 AMR AF: 0.0747

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.0819

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.107 Hom.: 181

Bravo AF: 0.0827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.2
CADD	Benign	5.8
DANN	Benign	0.53

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: rs1976930; hg19: chr12-131576445;