ADRA1B p.Pro325Thr

Variant names:

• chr5-159971902-C-A
• rs1195785055
• NM_000679.4:c.973C>A
• ADRA1B p.Pro325Thr

Your query was ambiguous. Multiple possible variants found:

• chr5-159971902-C-A
• chr5-159971902-CCC-ACT
• chr5-159971902-CCC-ACA
• chr5-159971902-CCC-ACG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000679.4(ADRA1B):​c.973C>A​(p.Pro325Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000004 in 999,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: ADRA1B NM_000679.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.81
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.973C>A	p.Pro325Thr	missense	Exon 2 of 2	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.973C>A	p.Pro325Thr	missense	Exon 2 of 2	ENSP00000306662.3	P35368
	ADRA1B	ENST00000865014.1		c.973C>A	p.Pro325Thr	missense	Exon 5 of 5	ENSP00000535073.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000400 AC: 4 AN: 999550 Hom.: 0 Cov.: 40 AF XY: 0.00000207 AC XY: 1 AN XY: 483414

African (AFR) AF: 0.00 AC: 0 AN: 20096

American (AMR) AF: 0.00 AC: 0 AN: 14664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11426

East Asian (EAS) AF: 0.00 AC: 0 AN: 13374

South Asian (SAS) AF: 0.00 AC: 0 AN: 35122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3776

European-Non Finnish (NFE) AF: 0.00000476 AC: 4 AN: 840878

Other (OTH) AF: 0.00 AC: 0 AN: 35244

GnomAD4 genome Cov.: 29

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D
Eigen	Benign	0.17
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.31
Sift	Benign	0.082	T
Sift4G	Benign	0.15	T
Varity_R		0.56
gMVP		0.66
Mutation Taster		=62/38	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1195785055; hg19: chr5-159398909;