rs11953285

Positions:

• chr5-159964804-A-C

Variant summary

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

The NM_000679.4(ADRA1B):​c.950-7075A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,224 control chromosomes in the GnomAD database, including 997 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 0.10 (997 hom., cov: 32)
• Consequence: ADRA1B NM_000679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1B	NM_000679.4	c.950-7075A>C		intron_variant		ENST00000306675.5	NP_000670.1
ADRA1B	XM_006714821.4	c.950-20867A>C		intron_variant			XP_006714884.1
ADRA1B	XM_011534435.2	c.1058-7075A>C		intron_variant			XP_011532737.1
ADRA1B	XM_047416776.1	c.1058-7075A>C		intron_variant			XP_047272732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000306675.5	c.950-7075A>C		intron_variant		1	NM_000679.4	ENSP00000306662	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15715 AN: 152106 Hom.: 1001 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0894

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.103 AC: 15702 AN: 152224 Hom.: 997 Cov.: 32 AF XY: 0.103 AC XY: 7631 AN XY: 74424

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.130

Alfa AF: 0.127 Hom.: 699

Bravo AF: 0.0983

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.064
DANN	Benign	0.60

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: rs11953285; hg19: chr5-159391811;