5-159924453-C-T

Variant names:

• chr5-159924453-C-T
• rs756275
• NM_000679.4:c.949+6599C>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+6599C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 151,844 control chromosomes in the GnomAD database, including 386 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 0.068 (386 hom., cov: 32)
• Consequence: ADRA1B NM_000679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 4 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]

LINC01847 (HGNC:52662): (long intergenic non-protein coding RNA 1847)

ENSG00000306315 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1B	NM_000679.4	c.949+6599C>T		intron_variant	Intron 1 of 1	ENST00000306675.5	NP_000670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000306675.5	c.949+6599C>T		intron_variant	Intron 1 of 1	1	NM_000679.4	ENSP00000306662.3
LINC01847	ENST00000641163.1	n.181+4582G>A		intron_variant	Intron 2 of 7
LINC01847	ENST00000816795.1	n.142+4582G>A		intron_variant	Intron 2 of 3
ENSG00000306315	ENST00000816922.1	n.53-1036C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10331 AN: 151728 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.0555

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0348

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0768

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0680 AC: 10329 AN: 151844 Hom.: 386 Cov.: 32 AF XY: 0.0669 AC XY: 4963 AN XY: 74172

African (AFR) AF: 0.0524 AC: 2167 AN: 41376

American (AMR) AF: 0.0555 AC: 847 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.122 AC: 629 AN: 5164

South Asian (SAS) AF: 0.122 AC: 583 AN: 4784

European-Finnish (FIN) AF: 0.0348 AC: 366 AN: 10516

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0768 AC: 5219 AN: 67956

Other (OTH) AF: 0.0735 AC: 155 AN: 2108

Alfa AF: 0.0774 Hom.: 959

Bravo AF: 0.0679

Asia WGS AF: 0.103 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.82
PhyloP100		-0.19
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: rs756275; hg19: chr5-159351460;