rs12257731

chr10-133127635-G-Achr10-133127635-G-C

Variant summary

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

The NM_001083909.3(ADGRA1):c.500+304G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,086 control chromosomes in the GnomAD database, including 3,112 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 0.19 (3112 hom., cov: 33)
• Consequence: ADGRA1 NM_001083909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRA1	NM_001083909.3	c.500+304G>A		intron_variant		ENST00000392607.8
ADGRA1	NM_001291085.2	c.209+304G>A		intron_variant
ADGRA1	XM_011540273.1	c.-8+304G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRA1	ENST00000392607.8	c.500+304G>A		intron_variant		5	NM_001083909.3	P1
ADGRA1	ENST00000392606.2	c.209+304G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28384 AN: 151968 Hom.: 3104 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.187 AC: 28410 AN: 152086 Hom.: 3112 Cov.: 33 AF XY: 0.194 AC XY: 14414 AN XY: 74322

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.185

Alfa AF: 0.161 Hom.: 418

Bravo AF: 0.199

Asia WGS AF: 0.350 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.47
Dann	Benign	0.90

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: rs12257731; hg19: chr10-134941139;