chr10-133088810-A-T

Variant names:

• chr10-133088810-A-T
• rs10745302
• NM_001083909.3:c.-100A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001083909.3(ADGRA1):​c.-100A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 36)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADGRA1 NM_001083909.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADGRA1	NM_001083909.3	c.-100A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 7	ENST00000392607.8	NP_001077378.1
ADGRA1	NM_001083909.3	c.-100A>T		5_prime_UTR_variant	Exon 2 of 7	ENST00000392607.8	NP_001077378.1
ADGRA1	XM_017016779.2	c.-100A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5		XP_016872268.1
ADGRA1	XM_017016779.2	c.-100A>T		5_prime_UTR_variant	Exon 1 of 5		XP_016872268.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADGRA1	ENST00000392607.8	c.-100A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 7	5	NM_001083909.3	ENSP00000376384.3
ADGRA1	ENST00000392607.8	c.-100A>T		5_prime_UTR_variant	Exon 2 of 7	5	NM_001083909.3	ENSP00000376384.3

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1081648 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 510774

African (AFR) AF: 0.00 AC: 0 AN: 22992

American (AMR) AF: 0.00 AC: 0 AN: 8416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14376

East Asian (EAS) AF: 0.00 AC: 0 AN: 26514

South Asian (SAS) AF: 0.00 AC: 0 AN: 19500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919912

Other (OTH) AF: 0.00 AC: 0 AN: 43748

GnomAD4 genome Cov.: 36

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	0.88
PhyloP100		-0.12

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: rs10745302; hg19: chr10-134902314;