rs952037

Variant names:

• chr5-159963870-C-T
• rs952037
• NM_000679.4:c.950-8009C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000679.4(ADRA1B):​c.950-8009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,078 control chromosomes in the GnomAD database, including 9,978 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 0.35 (9978 hom., cov: 32)
• Consequence: ADRA1B NM_000679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 12 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1B	NM_000679.4	c.950-8009C>T		intron_variant	Intron 1 of 1	ENST00000306675.5	NP_000670.1
ADRA1B	XM_011534435.2	c.1058-8009C>T		intron_variant	Intron 4 of 4		XP_011532737.1
ADRA1B	XM_047416776.1	c.1058-8009C>T		intron_variant	Intron 5 of 5		XP_047272732.1
ADRA1B	XM_006714821.4	c.950-21801C>T		intron_variant	Intron 1 of 1		XP_006714884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000306675.5	c.950-8009C>T		intron_variant	Intron 1 of 1	1	NM_000679.4	ENSP00000306662.3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53433 AN: 151960 Hom.: 9961 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.352 AC: 53488 AN: 152078 Hom.: 9978 Cov.: 32 AF XY: 0.352 AC XY: 26137 AN XY: 74326

African (AFR) AF: 0.463 AC: 19211 AN: 41478

American (AMR) AF: 0.285 AC: 4353 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3472

East Asian (EAS) AF: 0.444 AC: 2294 AN: 5164

South Asian (SAS) AF: 0.399 AC: 1922 AN: 4822

European-Finnish (FIN) AF: 0.293 AC: 3092 AN: 10564

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20563 AN: 67970

Other (OTH) AF: 0.363 AC: 766 AN: 2112

Alfa AF: 0.316 Hom.: 17252

Bravo AF: 0.355

Asia WGS AF: 0.420 AC: 1459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.18
DANN	Benign	0.88
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs952037; hg19: chr5-159390877;