chr5-159940107-C-T

Variant names:

• chr5-159940107-C-T
• rs6888306
• NM_000679.4:c.949+22253C>T

Variant summary

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

The ENST00000306675.5(ADRA1B):​c.949+22253C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,068 control chromosomes in the GnomAD database, including 5,280 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 0.26 (5280 hom., cov: 32)
• Consequence: ADRA1B ENST00000306675.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000306675.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	NM_000679.4	MANE Select	c.949+22253C>T		intron	N/A	NP_000670.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	ENST00000306675.5	TSL:1 MANE Select	c.949+22253C>T		intron	N/A	ENSP00000306662.3

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39678 AN: 151950 Hom.: 5273 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.261 AC: 39724 AN: 152068 Hom.: 5280 Cov.: 32 AF XY: 0.263 AC XY: 19582 AN XY: 74322

African (AFR) AF: 0.294 AC: 12200 AN: 41498

American (AMR) AF: 0.242 AC: 3694 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 810 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2046 AN: 5160

South Asian (SAS) AF: 0.242 AC: 1165 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2835 AN: 10572

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16101 AN: 67966

Other (OTH) AF: 0.253 AC: 533 AN: 2106

Alfa AF: 0.241 Hom.: 14289

Bravo AF: 0.259

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		0.54
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: rs6888306; hg19: chr5-159367114;