chr10-133105348-C-T

Position:

• chr10-133105348-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRA1	NM_001083909.3	c.401+2506C>T		intron_variant		ENST00000392607.8	NP_001077378.1
ADGRA1	XM_017016779.2	c.733C>T	p.Pro245Ser	missense_variant	5/5		XP_016872268.1
ADGRA1	NM_001291085.2	c.110+2506C>T		intron_variant			NP_001278014.1
ADGRA1	XM_011540273.1	c.-107+6585C>T		intron_variant			XP_011538575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8	c.401+2506C>T		intron_variant		5	NM_001083909.3	ENSP00000376384.3
ADGRA1	ENST00000392606.2	c.110+2506C>T		intron_variant		1		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

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.244

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.48

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: rs11101932; hg19: chr10-134918852;