8-26864508-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_000680.4(ADRA1A):c.462C>G(p.Ser154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,614,026 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (64 hom.)
• Consequence: ADRA1A NM_000680.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.106

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 8-26864508-G-C is Benign according to our data. Variant chr8-26864508-G-C is described in ClinVar as [Benign]. Clinvar id is 775260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.106 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.462C>G	p.Ser154=	synonymous_variant	2/3	ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.462C>G	p.Ser154=	synonymous_variant	2/3	2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.00566 AC: 861 AN: 152190 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00789

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00719 AC: 1806 AN: 251186 Hom.: 11 AF XY: 0.00783 AC XY: 1063 AN XY: 135776

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00754

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0109

Gnomad FIN exome AF: 0.0139

Gnomad NFE exome AF: 0.00815

Gnomad OTH exome AF: 0.00670

GnomAD4 exome AF: 0.00774 AC: 11316 AN: 1461718 Hom.: 64 Cov.: 31 AF XY: 0.00782 AC XY: 5689 AN XY: 727162

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00315

Gnomad4 ASJ exome AF: 0.00700

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0109

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.00794

Gnomad4 OTH exome AF: 0.00638

GnomAD4 genome AF: 0.00565 AC: 861 AN: 152308 Hom.: 3 Cov.: 32 AF XY: 0.00565 AC XY: 421 AN XY: 74478

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.00789

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00658 Hom.: 0

Bravo AF: 0.00451

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00742

EpiControl AF: 0.00729

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

Jul 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	7.0
Dann	Benign	0.72

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: rs2229124; hg19: chr8-26722025;