NM_000679.4:c.949+15624G>T

Variant names:

• chr5-159933478-G-T
• rs6892282
• NM_000679.4:c.949+15624G>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+15624G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,062 control chromosomes in the GnomAD database, including 15,938 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 0.45 (15938 hom., cov: 33)
• Consequence: ADRA1B NM_000679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• 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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	NM_000679.4	MANE Select	c.949+15624G>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+15624G>T		intron	N/A	ENSP00000306662.3
	LINC01847	ENST00000641163.1		n.118+4171C>A		intron	N/A
	LINC01847	ENST00000816795.1		n.79+4171C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68826 AN: 151944 Hom.: 15913 Cov.: 33

Gnomad AFR AF: 0.451

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.453 AC: 68892 AN: 152062 Hom.: 15938 Cov.: 33 AF XY: 0.455 AC XY: 33799 AN XY: 74318

African (AFR) AF: 0.451 AC: 18693 AN: 41466

American (AMR) AF: 0.445 AC: 6792 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1417 AN: 3466

East Asian (EAS) AF: 0.740 AC: 3825 AN: 5172

South Asian (SAS) AF: 0.425 AC: 2051 AN: 4828

European-Finnish (FIN) AF: 0.438 AC: 4630 AN: 10562

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29951 AN: 67972

Other (OTH) AF: 0.454 AC: 957 AN: 2110

Alfa AF: 0.443 Hom.: 45831

Bravo AF: 0.451

Asia WGS AF: 0.553 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.78
PhyloP100		0.29
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: rs6892282; hg19: chr5-159360485; COSMIC: COSV60701035;