chr8-26863764-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000680.4(ADRA1A):​c.883+323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,070 control chromosomes in the GnomAD database, including 10,150 homozygotes. 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: 𝑓 0.36 ( 10150 hom., cov: 32)

Consequence

ADRA1A
NM_000680.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.638

Publications

8 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADRA1ANM_000680.4 linkc.883+323T>C intron_variant Intron 2 of 2 ENST00000380573.4 NP_000671.2 P35348-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADRA1AENST00000380573.4 linkc.883+323T>C intron_variant Intron 2 of 2 2 NM_000680.4 ENSP00000369947.3 P35348-1

Frequencies

GnomAD3 genomes
AF:
0.358
AC:
54457
AN:
151952
Hom.:
10142
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.245
Gnomad AMI
AF:
0.417
Gnomad AMR
AF:
0.389
Gnomad ASJ
AF:
0.454
Gnomad EAS
AF:
0.366
Gnomad SAS
AF:
0.289
Gnomad FIN
AF:
0.398
Gnomad MID
AF:
0.383
Gnomad NFE
AF:
0.412
Gnomad OTH
AF:
0.386
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.358
AC:
54499
AN:
152070
Hom.:
10150
Cov.:
32
AF XY:
0.353
AC XY:
26251
AN XY:
74326
show subpopulations
African (AFR)
AF:
0.246
AC:
10197
AN:
41506
American (AMR)
AF:
0.389
AC:
5951
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.454
AC:
1577
AN:
3472
East Asian (EAS)
AF:
0.366
AC:
1887
AN:
5158
South Asian (SAS)
AF:
0.291
AC:
1401
AN:
4822
European-Finnish (FIN)
AF:
0.398
AC:
4206
AN:
10566
Middle Eastern (MID)
AF:
0.384
AC:
113
AN:
294
European-Non Finnish (NFE)
AF:
0.412
AC:
27981
AN:
67952
Other (OTH)
AF:
0.383
AC:
807
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1793
3586
5378
7171
8964
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
526
1052
1578
2104
2630
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.392
Hom.:
38190
Bravo
AF:
0.356
Asia WGS
AF:
0.323
AC:
1122
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
8.5
DANN
Benign
0.61
PhyloP100
0.64
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs573514; hg19: chr8-26721281; API