10-133093735-C-T

Variant names:

• chr10-133093735-C-T
• rs11101913
• NM_001083909.3:c.4-3239C>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.4-3239C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,158 control chromosomes in the GnomAD database, including 6,551 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 0.28 (6551 hom., cov: 33)
• Consequence: ADGRA1 NM_001083909.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRA1	NM_001083909.3	c.4-3239C>T		intron_variant	Intron 2 of 6	ENST00000392607.8	NP_001077378.1
ADGRA1	XM_017016779.2	c.4-3239C>T		intron_variant	Intron 1 of 4		XP_016872268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8	c.4-3239C>T		intron_variant	Intron 2 of 6	5	NM_001083909.3	ENSP00000376384.3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42477 AN: 152038 Hom.: 6545 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.279 AC: 42497 AN: 152158 Hom.: 6551 Cov.: 33 AF XY: 0.289 AC XY: 21494 AN XY: 74382

African (AFR) AF: 0.220 AC: 9146 AN: 41522

American (AMR) AF: 0.369 AC: 5640 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 755 AN: 3472

East Asian (EAS) AF: 0.624 AC: 3214 AN: 5150

South Asian (SAS) AF: 0.479 AC: 2313 AN: 4828

European-Finnish (FIN) AF: 0.297 AC: 3148 AN: 10590

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17340 AN: 67982

Other (OTH) AF: 0.279 AC: 588 AN: 2108

Alfa AF: 0.264 Hom.: 6722

Bravo AF: 0.279

Asia WGS AF: 0.518 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0070
DANN	Benign	0.44
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11101913; hg19: chr10-134907239;