Variant 5-159916983-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_000679.4(ADRA1B):c.78T>C(p.Thr26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,614,134 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 10 hom. )

Consequence

ADRA1B
NM_000679.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.953

Variant links:

Genes affected

ADRA1B (HGNC:278): (adrenoceptor alpha 1B) 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-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region. [provided by RefSeq, Jul 2008]

ADRA1B links:

LINC01847 (HGNC:52662): (long intergenic non-protein coding RNA 1847)

LINC01847 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 5-159916983-T-C is Benign according to our data. Variant chr5-159916983-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656007.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.953 with no splicing effect.

BS2

High AC in GnomAd4 at 42 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1B	NM_000679.4 linkuse as main transcript	c.78T>C	p.Thr26=	synonymous_variant	1/2	ENST00000306675.5	NP_000670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADRA1B	ENST00000306675.5 linkuse as main transcript	c.78T>C	p.Thr26=	synonymous_variant	1/2	1	NM_000679.4	ENSP00000306662	P1
LINC01847	ENST00000641163.1 linkuse as main transcript	n.181+12052A>G		intron_variant, non_coding_transcript_variant
ADRA1B	ENST00000641205.1 linkuse as main transcript	c.78T>C	p.Thr26=	synonymous_variant	3/3			ENSP00000493019

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00115

AC:

289

AN:

251364

Hom.:

AF XY:

0.00160

AC XY:

217

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00924

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000540

AC:

789

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000821

AC XY:

597

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00851

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.000276

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00809

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.0000378

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

ADRA1B: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.7

DANN

Benign

0.71

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over