8-26769732-G-T

Variant names:

• chr8-26769732-G-T
• rs3739216
• NM_000680.4:c.*417C>A

Variant summary

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

The NM_000680.4(ADRA1A):​c.*417C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000239 in 838,116 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: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: ADRA1A NM_000680.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 10 publications found

Genes affected

ADRA1A (HGNC:277): (adrenoceptor alpha 1A) Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferation of many cells. There are 3 alpha-1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. This gene encodes alpha-1A-adrenergic receptor. Alternative splicing of this gene generates four transcript variants, which encode four different isoforms with distinct C-termini but having similar ligand binding properties. [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_000680.4. 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
	ADRA1A	NM_000680.4	MANE Select	c.*417C>A		3_prime_UTR	Exon 3 of 3	NP_000671.2
	ADRA1A	NM_033303.4		c.1269+549C>A		intron	N/A	NP_150646.3
	ADRA1A	NM_033304.3		c.1269+549C>A		intron	N/A	NP_150647.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.*417C>A		3_prime_UTR	Exon 3 of 3	ENSP00000369947.3
	ADRA1A	ENST00000276393.8	TSL:1	c.*417C>A		3_prime_UTR	Exon 2 of 2	ENSP00000276393.4
	ADRA1A	ENST00000380586.5	TSL:1	c.1269+549C>A		intron	N/A	ENSP00000369960.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000239 AC: 2 AN: 838116 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 387180

African (AFR) AF: 0.00 AC: 0 AN: 15928

American (AMR) AF: 0.00 AC: 0 AN: 1394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5342

East Asian (EAS) AF: 0.00 AC: 0 AN: 3746

South Asian (SAS) AF: 0.00 AC: 0 AN: 16548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1630

European-Non Finnish (NFE) AF: 0.00000261 AC: 2 AN: 765508

Other (OTH) AF: 0.00 AC: 0 AN: 27602

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.58
DANN	Benign	0.62
PhyloP100		-0.27

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: rs3739216; hg19: chr8-26627249;