10-133098810-G-A

Variant names:

• chr10-133098810-G-A
• rs11101916
• NM_001083909.3:c.255+47G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392607.8(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 ENST00000392607.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392607.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA1	NM_001083909.3	MANE Select	c.255+47G>A		intron	N/A	NP_001077378.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA1	ENST00000392607.8	TSL:5 MANE Select	c.255+47G>A		intron	N/A	ENSP00000376384.3

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

GnomAD2 exomes AF: 0.151 AC: 34055 AN: 225294 AF XY: 0.154

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 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

African (AFR) AF: 0.0842 AC: 2706 AN: 32134

American (AMR) AF: 0.102 AC: 4005 AN: 39404

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5161 AN: 24922

East Asian (EAS) AF: 0.0882 AC: 3451 AN: 39110

South Asian (SAS) AF: 0.124 AC: 10323 AN: 82990

European-Finnish (FIN) AF: 0.167 AC: 7450 AN: 44652

Middle Eastern (MID) AF: 0.161 AC: 905 AN: 5616

European-Non Finnish (NFE) AF: 0.179 AC: 196247 AN: 1096544

Other (OTH) AF: 0.166 AC: 9825 AN: 59034

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

African (AFR) AF: 0.0810 AC: 3366 AN: 41572

American (AMR) AF: 0.141 AC: 2153 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.106 AC: 550 AN: 5188

South Asian (SAS) AF: 0.121 AC: 585 AN: 4826

European-Finnish (FIN) AF: 0.160 AC: 1693 AN: 10602

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12136 AN: 68014

Other (OTH) AF: 0.167 AC: 353 AN: 2116

Alfa AF: 0.154 Hom.: 1188

Bravo AF: 0.141

Asia WGS AF: 0.103 AC: 362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.9
DANN	Benign	0.77
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11101916; hg19: chr10-134912314; COSMIC: COSV66925752; COSMIC: COSV66925752;