Variant 8-26866167-C-T details in Genebe, Genetics Data Aggregator

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

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]

ADRA1A links:

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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
ADRA1A	NM_000680.4 link	c.-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
ADRA1A	ENST00000380573.4 link	c.-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.:

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.:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over