NM_000674.3:c.342-23C>A

Variant names:

• chr1-203165238-C-A
• rs200347485
• NM_000674.3:c.342-23C>A

Variant summary

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

The NM_000674.3(ADORA1):​c.342-23C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 0 publications found

Genes affected

ADORA1 (HGNC:262): (adenosine A1 receptor) The protein encoded by this gene is an adenosine receptor that belongs to the G-protein coupled receptor 1 family. There are 3 types of adenosine receptors, each with a specific pattern of ligand binding and tissue distribution, and together they regulate a diverse set of physiologic functions. The type A1 receptors inhibit adenylyl cyclase, and play a role in the fertilization process. Animal studies also suggest a role for A1 receptors in kidney function and ethanol intoxication. Transcript variants with alternative splicing in the 5' UTR have been found for this gene. [provided by RefSeq, Jul 2008]

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=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000674.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	NM_000674.3	MANE Select	c.342-23C>A		intron	N/A	NP_000665.1	P30542-1
	ADORA1	NM_001365065.1		c.115C>A	p.His39Asn	missense	Exon 3 of 3	NP_001351994.1	B7Z1L9
	ADORA1	NM_001048230.2		c.342-23C>A		intron	N/A	NP_001041695.1	P30542-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	ENST00000337894.9	TSL:2 MANE Select	c.342-23C>A		intron	N/A	ENSP00000338435.4	P30542-1
	ADORA1	ENST00000309502.7	TSL:1	c.342-23C>A		intron	N/A	ENSP00000308549.3	P30542-1
	ADORA1	ENST00000367236.8	TSL:1	c.342-23C>A		intron	N/A	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444874 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717338

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32774

American (AMR) AF: 0.00 AC: 0 AN: 42152

Ashkenazi Jewish (ASJ) AF: 0.0000398 AC: 1 AN: 25138

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.00 AC: 0 AN: 84074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5668

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103144

Other (OTH) AF: 0.00 AC: 0 AN: 59490

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.68
PhyloP100		-0.33

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: rs200347485; hg19: chr1-203134366;