rs949956077

Variant names:

• chr12-130992264-A-C
• rs949956077
• NM_198827.5:c.838A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-130992264-A-C
• chr12-130992264-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198827.5(ADGRD1):​c.838A>C​(p.Ile280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I280V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ADGRD1 NM_198827.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93
• Publications: 0 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]

ADGRD1-AS1 (HGNC:53314): (ADGRD1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28755182).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198827.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRD1	NM_198827.5	MANE Select	c.838A>C	p.Ile280Leu	missense	Exon 8 of 25	NP_942122.2
	ADGRD1	NM_001330497.2		c.934A>C	p.Ile312Leu	missense	Exon 9 of 26	NP_001317426.1	Q6QNK2-4
	ADGRD1-AS1	NR_131950.1		n.277+85T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRD1	ENST00000261654.10	TSL:1 MANE Select	c.838A>C	p.Ile280Leu	missense	Exon 8 of 25	ENSP00000261654.5	Q6QNK2-1
	ADGRD1	ENST00000535015.5	TSL:1	c.934A>C	p.Ile312Leu	missense	Exon 9 of 26	ENSP00000444425.1	Q6QNK2-4
	ADGRD1	ENST00000881063.1		c.838A>C	p.Ile280Leu	missense	Exon 8 of 26	ENSP00000551122.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250806 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461184 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726826

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111798

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.023
Eigen_PC	Benign	0.0011
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.9
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.18
Sift	Benign	0.063	T
Sift4G	Uncertain	0.021	D
Polyphen		0.86	P
Vest4		0.26
MutPred		0.49		Loss of helix (P = 0.0123)
MVP		0.40
MPC		0.18
ClinPred		0.58	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.40
Mutation Taster		=87/13	polymorphism

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: rs949956077; hg19: chr12-131476809;