rs10053468

Variant names:

• chr5-159980157-A-C
• rs10053468
• XM_006714821.4:c.950-5514A>C

Variant summary

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

The XM_006714821.4(ADRA1B):​c.950-5514A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,896 control chromosomes in the GnomAD database, including 2,327 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 0.14 (2327 hom., cov: 31)
• Consequence: ADRA1B XM_006714821.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1B	XM_006714821.4	c.950-5514A>C		intron_variant	Intron 1 of 1		XP_006714884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21052 AN: 151778 Hom.: 2314 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.0845

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.139 AC: 21113 AN: 151896 Hom.: 2327 Cov.: 31 AF XY: 0.136 AC XY: 10080 AN XY: 74248

African (AFR) AF: 0.307 AC: 12703 AN: 41342

American (AMR) AF: 0.0975 AC: 1488 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0845 AC: 293 AN: 3468

East Asian (EAS) AF: 0.145 AC: 741 AN: 5128

South Asian (SAS) AF: 0.0980 AC: 472 AN: 4816

European-Finnish (FIN) AF: 0.0388 AC: 411 AN: 10598

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0680 AC: 4619 AN: 67964

Other (OTH) AF: 0.124 AC: 261 AN: 2110

Alfa AF: 0.0907 Hom.: 2584

Bravo AF: 0.151

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-0.098

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10053468; hg19: chr5-159407164;