Genetic Variant ADRA1B:p.Ile178Ile (chr5-159917439-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_000679.4(ADRA1B):c.534C>T(p.Ile178Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,614,144 control chromosomes in the GnomAD database, including 881 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 0.026 ( 79 hom., cov: 32)

Exomes 𝑓: 0.030 ( 802 hom. )

Consequence

ADRA1B
NM_000679.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=-0.34 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0263 (4007/152254) while in subpopulation NFE AF= 0.0362 (2463/68022). AF 95% confidence interval is 0.035. There are 79 homozygotes in gnomad4. There are 1937 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4007 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1B	NM_000679.4 link	c.534C>T	p.Ile178Ile	synonymous_variant	Exon 1 of 2	ENST00000306675.5	NP_000670.1	P35368

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000306675.5 link	c.534C>T	p.Ile178Ile	synonymous_variant	Exon 1 of 2	1	NM_000679.4	ENSP00000306662.3		P35368
LINC01847	ENST00000641163.1 link	n.181+11596G>A		intron_variant	Intron 2 of 7

Frequencies

GnomAD3 genomes

AF:

0.0263

AC:

4008

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.0581

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0362

Gnomad OTH

AF:

0.0283

GnomAD3 exomes

AF:

0.0257

AC:

6466

AN:

251426

Hom.:

137

AF XY:

0.0260

AC XY:

3528

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.00931

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00826

Gnomad FIN exome

AF:

0.0588

Gnomad NFE exome

AF:

0.0363

Gnomad OTH exome

AF:

0.0248

GnomAD4 exome

AF:

0.0304

AC:

44450

AN:

1461890

Hom.:

802

Cov.:

AF XY:

0.0299

AC XY:

21720

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0116

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00898

Gnomad4 FIN exome

AF:

0.0556

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0270

GnomAD4 genome

AF:

0.0263

AC:

4007

AN:

152254

Hom.:

Cov.:

AF XY:

0.0260

AC XY:

1937

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0581

Gnomad4 NFE

AF:

0.0362

Gnomad4 OTH

AF:

0.0280

Alfa

AF:

0.0306

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0328

EpiControl

AF:

0.0296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.2

DANN

Benign

0.85

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over