rs11750092

Variant names:

• chr5-159940964-C-T
• rs11750092
• NM_000679.4:c.949+23110C>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.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
• Publications: 10 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 (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000679.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	NM_000679.4	MANE Select	c.949+23110C>T		intron	N/A	NP_000670.1	P35368

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	ENST00000306675.5	TSL:1 MANE Select	c.949+23110C>T		intron	N/A	ENSP00000306662.3	P35368
	ADRA1B	ENST00000865014.1		c.949+23110C>T		intron	N/A	ENSP00000535073.1

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

African (AFR) AF: 0.0741 AC: 3077 AN: 41528

American (AMR) AF: 0.103 AC: 1574 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3468

East Asian (EAS) AF: 0.0456 AC: 236 AN: 5170

South Asian (SAS) AF: 0.0906 AC: 437 AN: 4826

European-Finnish (FIN) AF: 0.231 AC: 2446 AN: 10570

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11130 AN: 68000

Other (OTH) AF: 0.132 AC: 278 AN: 2108

Alfa AF: 0.141 Hom.: 226

Bravo AF: 0.116

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.47
PhyloP100		-1.1
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: rs11750092; hg19: chr5-159367971;