10-133105348-C-T

Variant names:

• chr10-133105348-C-T
• rs11101932
• NM_001083909.3:c.401+2506C>T

Variant summary

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

The NM_001083909.3(ADGRA1):​c.401+2506C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,102 control chromosomes in the GnomAD database, including 5,354 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 0.24 (5354 hom., cov: 33)
• Consequence: ADGRA1 NM_001083909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083909.3. 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.401+2506C>T		intron	N/A	NP_001077378.1
	ADGRA1	NM_001291085.2		c.110+2506C>T		intron	N/A	NP_001278014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRA1	ENST00000392607.8	TSL:5 MANE Select	c.401+2506C>T		intron	N/A	ENSP00000376384.3
	ADGRA1	ENST00000392606.2	TSL:1	c.110+2506C>T		intron	N/A	ENSP00000376383.2

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36465 AN: 151984 Hom.: 5332 Cov.: 33

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.240 AC: 36528 AN: 152102 Hom.: 5354 Cov.: 33 AF XY: 0.247 AC XY: 18356 AN XY: 74356

African (AFR) AF: 0.350 AC: 14508 AN: 41480

American (AMR) AF: 0.295 AC: 4507 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3472

East Asian (EAS) AF: 0.547 AC: 2804 AN: 5128

South Asian (SAS) AF: 0.317 AC: 1525 AN: 4818

European-Finnish (FIN) AF: 0.177 AC: 1870 AN: 10594

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10144 AN: 68008

Other (OTH) AF: 0.244 AC: 515 AN: 2110

Alfa AF: 0.191 Hom.: 412

Bravo AF: 0.255

Asia WGS AF: 0.426 AC: 1478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.48
PhyloP100		0.60
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: rs11101932; hg19: chr10-134918852;