8-26866167-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_000680.4(ADRA1A):​c.-686-512G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,120 control chromosomes in the GnomAD database, including 59,168 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 0.88 ( 59168 hom., cov: 31)

Consequence

ADRA1A
NM_000680.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.822
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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADRA1ANM_000680.4 linkc.-686-512G>A intron_variant ENST00000380573.4 NP_000671.2 P35348-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADRA1AENST00000380573.4 linkc.-686-512G>A intron_variant 2 NM_000680.4 ENSP00000369947.3 P35348-1

Frequencies

GnomAD3 genomes
AF:
0.875
AC:
133053
AN:
152002
Hom.:
59147
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.705
Gnomad AMI
AF:
0.982
Gnomad AMR
AF:
0.875
Gnomad ASJ
AF:
0.986
Gnomad EAS
AF:
0.909
Gnomad SAS
AF:
0.932
Gnomad FIN
AF:
0.942
Gnomad MID
AF:
0.940
Gnomad NFE
AF:
0.954
Gnomad OTH
AF:
0.883
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.875
AC:
133126
AN:
152120
Hom.:
59168
Cov.:
31
AF XY:
0.877
AC XY:
65210
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.705
Gnomad4 AMR
AF:
0.874
Gnomad4 ASJ
AF:
0.986
Gnomad4 EAS
AF:
0.909
Gnomad4 SAS
AF:
0.933
Gnomad4 FIN
AF:
0.942
Gnomad4 NFE
AF:
0.954
Gnomad4 OTH
AF:
0.879
Alfa
AF:
0.909
Hom.:
7443
Bravo
AF:
0.862
Asia WGS
AF:
0.885
AC:
3080
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
8.3
DANN
Benign
0.96

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs574584; hg19: chr8-26723684; COSMIC: COSV52375152; COSMIC: COSV52375152; API