10-133088810-A-G

Position:

• chr10-133088810-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.-100A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,233,776 control chromosomes in the GnomAD database, including 188,776 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 0.64 (32756 hom., cov: 36)
  • Exomes 𝑓: 0.53 (156020 hom.)
• Consequence: ADGRA1 NM_001083909.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRA1	NM_001083909.3	c.-100A>G		5_prime_UTR_variant	2/7	ENST00000392607.8
ADGRA1	XM_017016779.2	c.-100A>G		5_prime_UTR_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA1	ENST00000392607.8	c.-100A>G		5_prime_UTR_variant	2/7	5	NM_001083909.3	P1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96802 AN: 152102 Hom.: 32694 Cov.: 36

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.532 AC: 575733 AN: 1081564 Hom.: 156020 Cov.: 40 AF XY: 0.533 AC XY: 272047 AN XY: 510740

Gnomad4 AFR exome AF: 0.895

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.765

Gnomad4 SAS exome AF: 0.635

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.512

Gnomad4 OTH exome AF: 0.568

GnomAD4 genome AF: 0.637 AC: 96921 AN: 152212 Hom.: 32756 Cov.: 36 AF XY: 0.637 AC XY: 47393 AN XY: 74396

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.640

Alfa AF: 0.578 Hom.: 3316

Bravo AF: 0.656

Asia WGS AF: 0.681 AC: 2363 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.84

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: rs10745302; hg19: chr10-134902314;