ENST00000354550.4:c.*184C>T

Variant names:

• chr8-26765867-G-A
• rs3802241
• ENST00000354550.4:c.*184C>T

Variant summary

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

The ENST00000354550.4(ADRA1A):​c.*184C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,403,252 control chromosomes in the GnomAD database, including 163,846 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 0.55 (24769 hom., cov: 33)
  • Exomes 𝑓: 0.46 (139077 hom.)
• Consequence: ADRA1A ENST00000354550.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 11 publications found

Genes affected

ADRA1A (HGNC:277): (adrenoceptor alpha 1A) 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-1A-adrenergic receptor. Alternative splicing of this gene generates four transcript variants, which encode four different isoforms with distinct C-termini but having similar ligand binding properties. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354550.4. 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
	ADRA1A	NM_033304.3		c.*184C>T		3_prime_UTR	Exon 3 of 3	NP_150647.2	P35348-4
	ADRA1A	NM_033303.4		c.1269+4414C>T		intron	N/A	NP_150646.3	B0ZBD3
	ADRA1A	NM_033302.3		c.1269+4414C>T		intron	N/A	NP_150645.2	P35348-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000354550.4	TSL:1	c.*184C>T		3_prime_UTR	Exon 3 of 3	ENSP00000346557.4	P35348-4
	ADRA1A	ENST00000380586.5	TSL:1	c.1269+4414C>T		intron	N/A	ENSP00000369960.1	P35348-2
	ADRA1A	ENST00000380582.7	TSL:1	c.1269+4414C>T		intron	N/A	ENSP00000369956.3	P35348-3

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83313 AN: 151976 Hom.: 24743 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.543

GnomAD4 exome AF: 0.461 AC: 577041 AN: 1251158 Hom.: 139077 Cov.: 31 AF XY: 0.462 AC XY: 278963 AN XY: 603590

African (AFR) AF: 0.767 AC: 21310 AN: 27798

American (AMR) AF: 0.499 AC: 9535 AN: 19118

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 8764 AN: 18038

East Asian (EAS) AF: 0.886 AC: 30057 AN: 33928

South Asian (SAS) AF: 0.534 AC: 28589 AN: 53552

European-Finnish (FIN) AF: 0.347 AC: 10165 AN: 29304

Middle Eastern (MID) AF: 0.535 AC: 1986 AN: 3714

European-Non Finnish (NFE) AF: 0.434 AC: 440275 AN: 1013724

Other (OTH) AF: 0.507 AC: 26360 AN: 51982

GnomAD4 genome AF: 0.548 AC: 83386 AN: 152094 Hom.: 24769 Cov.: 33 AF XY: 0.545 AC XY: 40553 AN XY: 74362

African (AFR) AF: 0.752 AC: 31214 AN: 41484

American (AMR) AF: 0.530 AC: 8102 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1676 AN: 3472

East Asian (EAS) AF: 0.894 AC: 4628 AN: 5174

South Asian (SAS) AF: 0.560 AC: 2696 AN: 4814

European-Finnish (FIN) AF: 0.335 AC: 3543 AN: 10588

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.440 AC: 29885 AN: 67958

Other (OTH) AF: 0.543 AC: 1147 AN: 2114

Alfa AF: 0.475 Hom.: 22090

Bravo AF: 0.569

Asia WGS AF: 0.695 AC: 2415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	13
DANN	Benign	0.66
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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: rs3802241;

hg19: chr8-26623384;