8-26864151-C-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000680.4(ADRA1A):c.819G>T(p.Thr273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,614,128 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (8 hom.)
• Consequence: ADRA1A NM_000680.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.791

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

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 8-26864151-C-A is Benign according to our data. Variant chr8-26864151-C-A is described in ClinVar as [Benign]. Clinvar id is 782112.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.791 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.819G>T	p.Thr273=	synonymous_variant	2/3	ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.819G>T	p.Thr273=	synonymous_variant	2/3	2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00160 AC: 402 AN: 251182 Hom.: 1 AF XY: 0.00168 AC XY: 228 AN XY: 135834

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000752

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00282

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00216 AC: 3160 AN: 1461824 Hom.: 8 Cov.: 31 AF XY: 0.00212 AC XY: 1543 AN XY: 727216

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.000827

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.000412

Gnomad4 NFE exome AF: 0.00260

Gnomad4 OTH exome AF: 0.00161

GnomAD4 genome AF: 0.00156 AC: 238 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74472

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00245

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00186 Hom.: 0

Bravo AF: 0.00150

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00279

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 28, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	2.7
Dann	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs61757007; hg19: chr8-26721668; COSMIC: COSV52359123;