rs11750092

Positions:

• chr5-159940964-C-T

Variant summary

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

The NM_000679.4(ADRA1B):​c.949+23110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,152 control chromosomes in the GnomAD database, including 1,496 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 0.13 (1496 hom., cov: 32)
• Consequence: ADRA1B NM_000679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1B	NM_000679.4	c.949+23110C>T		intron_variant		ENST00000306675.5	NP_000670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000306675.5	c.949+23110C>T		intron_variant		1	NM_000679.4	ENSP00000306662.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19857 AN: 152034 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0457

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.131 AC: 19859 AN: 152152 Hom.: 1496 Cov.: 32 AF XY: 0.132 AC XY: 9855 AN XY: 74388

Gnomad4 AFR AF: 0.0741

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0456

Gnomad4 SAS AF: 0.0906

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.132

Alfa AF: 0.145 Hom.: 225

Bravo AF: 0.116

Asia WGS AF: 0.0840 AC: 294 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	0.54
DANN	Benign	0.47

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: rs11750092; hg19: chr5-159367971;