rs11101916

Positions:

• chr10-133098810-G-A
• chr10-133098810-G-T

Variant summary

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

The NM_001083909.3(ADGRA1):​c.255+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,576,698 control chromosomes in the GnomAD database, including 22,799 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 0.14 (1697 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21102 hom.)
• Consequence: ADGRA1 NM_001083909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRA1	NM_001083909.3	c.255+47G>A		intron_variant		ENST00000392607.8
ADGRA1	XM_011540273.1	c.-107+47G>A		intron_variant
ADGRA1	XM_017016779.2	c.255+47G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA1	ENST00000392607.8	c.255+47G>A		intron_variant		5	NM_001083909.3	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21735 AN: 152174 Hom.: 1696 Cov.: 33

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.151 AC: 34055 AN: 225294 Hom.: 2750 AF XY: 0.154 AC XY: 18943 AN XY: 122920

Gnomad AFR exome AF: 0.0819

Gnomad AMR exome AF: 0.0985

Gnomad ASJ exome AF: 0.205

Gnomad EAS exome AF: 0.113

Gnomad SAS exome AF: 0.128

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.180

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.169 AC: 240073 AN: 1424406 Hom.: 21102 Cov.: 31 AF XY: 0.168 AC XY: 118772 AN XY: 706348

Gnomad4 AFR exome AF: 0.0842

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.0882

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.143 AC: 21743 AN: 152292 Hom.: 1697 Cov.: 33 AF XY: 0.141 AC XY: 10536 AN XY: 74476

Gnomad4 AFR AF: 0.0810

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.167

Alfa AF: 0.152 Hom.: 1065

Bravo AF: 0.141

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11101916; hg19: chr10-134912314; COSMIC: COSV66925752; COSMIC: COSV66925752;