Genetic Variant NM_000679.4:c.1101C>T (chr5-159972030-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_000679.4(ADRA1B):c.1101C>T(p.Cys367Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,400,436 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 29)

Exomes 𝑓: 0.0026 ( 5 hom. )

Consequence

ADRA1B
NM_000679.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.202

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 5-159972030-C-T is Benign according to our data. Variant chr5-159972030-C-T is described in ClinVar as Benign. ClinVar VariationId is 708372.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.202 with no splicing effect.

BS2

High AC in GnomAd4 at 299 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000679.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	NM_000679.4	MANE Select	c.1101C>T	p.Cys367Cys	synonymous	Exon 2 of 2	NP_000670.1	P35368

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	ENST00000306675.5	TSL:1 MANE Select	c.1101C>T	p.Cys367Cys	synonymous	Exon 2 of 2	ENSP00000306662.3	P35368
	ADRA1B	ENST00000865014.1		c.1101C>T	p.Cys367Cys	synonymous	Exon 5 of 5	ENSP00000535073.1

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

299

AN:

150976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00175

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00145

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00231

AC:

279

AN:

120892

AF XY:

0.00214

show subpopulations

Gnomad AFR exome

AF:

0.000894

Gnomad AMR exome

AF:

0.000980

Gnomad ASJ exome

AF:

0.00203

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00172

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.000791

GnomAD4 exome

AF:

0.00260

AC:

3248

AN:

1249352

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

1554

AN XY:

614840

show subpopulations

African (AFR)

AF:

0.000352

AC:

AN:

25560

American (AMR)

AF:

0.000642

AC:

AN:

18686

Ashkenazi Jewish (ASJ)

AF:

0.00163

AC:

AN:

19572

East Asian (EAS)

AF:

0.00

AC:

AN:

29728

South Asian (SAS)

AF:

0.000370

AC:

AN:

48590

European-Finnish (FIN)

AF:

0.00121

AC:

AN:

42820

Middle Eastern (MID)

AF:

0.000205

AC:

AN:

4872

European-Non Finnish (NFE)

AF:

0.00300

AC:

3024

AN:

1009510

Other (OTH)

AF:

0.00200

AC:

100

AN:

50014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

194

389

583

778

972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00198

AC:

299

AN:

151084

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

142

AN XY:

73812

show subpopulations

African (AFR)

AF:

0.000652

AC:

AN:

41416

American (AMR)

AF:

0.00184

AC:

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.00175

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00145

AC:

AN:

10314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00326

AC:

220

AN:

67448

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00279

Hom.:

Bravo

AF:

0.00141

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.2

(source)

DANN

Benign

0.95

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over