rs2030373

chr5-159920474-C-Achr5-159920474-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000679.4(ADRA1B):c.949+2620C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,958 control chromosomes in the GnomAD database, including 5,649 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 0.26 (5649 hom., cov: 32)
• Consequence: ADRA1B NM_000679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1B	NM_000679.4	c.949+2620C>A		intron_variant		ENST00000306675.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1B	ENST00000306675.5	c.949+2620C>A		intron_variant		1	NM_000679.4	P1
LINC01847	ENST00000641163.1	n.181+8561G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39964 AN: 151840 Hom.: 5645 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 39985 AN: 151958 Hom.: 5649 Cov.: 32 AF XY: 0.265 AC XY: 19698 AN XY: 74254

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.265

Alfa AF: 0.257 Hom.: 10195

Bravo AF: 0.271

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.4
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs2030373; hg19: chr5-159347481;