rs761777

Positions:

• chr10-133124571-A-G

Variant summary

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

The NM_001083909.3(ADGRA1):​c.402-2662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,230 control chromosomes in the GnomAD database, including 3,847 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 0.21 (3847 hom., cov: 33)
• Consequence: ADGRA1 NM_001083909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

Genes affected

ADGRA1 (HGNC:13838): (adhesion G protein-coupled receptor A1) This gene encodes a protein that belongs to the adhesion family of G-protein-coupled receptors. Members of this family function in several sensory systems and regulate blood pressure, immune responses, food intake and development. A similar protein in rodents is thought to play a role in in the regulation of neuronal signaling pathways. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA1	NM_001083909.3	c.402-2662A>G		intron_variant		ENST00000392607.8	NP_001077378.1
ADGRA1	NM_001291085.2	c.111-2662A>G		intron_variant			NP_001278014.1
ADGRA1	XM_011540273.1	c.-106-2662A>G		intron_variant			XP_011538575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8	c.402-2662A>G		intron_variant		5	NM_001083909.3	ENSP00000376384	P1
ADGRA1	ENST00000392606.2	c.111-2662A>G		intron_variant		1		ENSP00000376383

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31581 AN: 152112 Hom.: 3838 Cov.: 33

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.208 AC: 31597 AN: 152230 Hom.: 3847 Cov.: 33 AF XY: 0.209 AC XY: 15569 AN XY: 74416

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0973

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.238

Alfa AF: 0.228 Hom.: 697

Bravo AF: 0.204

Asia WGS AF: 0.118 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.26

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: rs761777; hg19: chr10-134938075;