5-159917729-C-T

Variant names:

• chr5-159917729-C-T
• rs1379488148
• NM_000679.4:c.824C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000679.4(ADRA1B):​c.824C>T​(p.Pro275Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P275R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ADRA1B NM_000679.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17340457).

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.824C>T	p.Pro275Leu	missense	Exon 1 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.824C>T	p.Pro275Leu	missense	Exon 1 of 2	ENSP00000306662.3	P35368
	ADRA1B	ENST00000865014.1		c.824C>T	p.Pro275Leu	missense	Exon 4 of 5	ENSP00000535073.1
	LINC01847	ENST00000641163.1		n.181+11306G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251330 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461856 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.89
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.061
Sift	Benign	0.47	T
Sift4G	Benign	0.50	T
Polyphen		0.026	B
Vest4		0.17
MutPred		0.41		Loss of glycosylation at P275 (P = 0.0388)
MVP		0.76
MPC		0.46
ClinPred		0.58	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.75
Mutation Taster		=83/17	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

Other links and lift over

dbSNP: rs1379488148; hg19: chr5-159344736;