rs1383914

Variant names:

• chr8-26865532-T-C
• rs1383914
• NM_000680.4:c.-563A>G

Variant summary

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

The NM_000680.4(ADRA1A):​c.-563A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 991,098 control chromosomes in the GnomAD database, including 120,081 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 0.48 (17339 hom., cov: 31)
  • Exomes 𝑓: 0.49 (102742 hom.)
• Consequence: ADRA1A NM_000680.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 19 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000680.4. 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_000680.4	MANE Select	c.-563A>G		5_prime_UTR	Exon 2 of 3	NP_000671.2	P35348-1
	ADRA1A	NM_033303.4		c.-563A>G		5_prime_UTR	Exon 1 of 3	NP_150646.3	B0ZBD3
	ADRA1A	NM_033304.3		c.-563A>G		5_prime_UTR	Exon 1 of 3	NP_150647.2	P35348-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.-563A>G		5_prime_UTR	Exon 2 of 3	ENSP00000369947.3	P35348-1
	ADRA1A	ENST00000380586.5	TSL:1	c.-563A>G		upstream_gene	N/A	ENSP00000369960.1	P35348-2
	ADRA1A	ENST00000276393.8	TSL:1	c.-563A>G		upstream_gene	N/A	ENSP00000276393.4	P35348-1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72311 AN: 151552 Hom.: 17329 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.494 AC: 415074 AN: 839428 Hom.: 102742 Cov.: 36 AF XY: 0.494 AC XY: 191740 AN XY: 388010

African (AFR) AF: 0.453 AC: 7172 AN: 15818

American (AMR) AF: 0.457 AC: 1207 AN: 2644

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 2587 AN: 5186

East Asian (EAS) AF: 0.541 AC: 2028 AN: 3750

South Asian (SAS) AF: 0.590 AC: 10089 AN: 17104

European-Finnish (FIN) AF: 0.489 AC: 174 AN: 356

Middle Eastern (MID) AF: 0.523 AC: 851 AN: 1628

European-Non Finnish (NFE) AF: 0.493 AC: 377386 AN: 765394

Other (OTH) AF: 0.493 AC: 13580 AN: 27548

GnomAD4 genome AF: 0.477 AC: 72350 AN: 151670 Hom.: 17339 Cov.: 31 AF XY: 0.484 AC XY: 35832 AN XY: 74072

African (AFR) AF: 0.448 AC: 18522 AN: 41354

American (AMR) AF: 0.457 AC: 6978 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1730 AN: 3472

East Asian (EAS) AF: 0.542 AC: 2763 AN: 5102

South Asian (SAS) AF: 0.603 AC: 2895 AN: 4800

European-Finnish (FIN) AF: 0.482 AC: 5059 AN: 10494

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32777 AN: 67876

Other (OTH) AF: 0.459 AC: 967 AN: 2108

Alfa AF: 0.483 Hom.: 56991

Bravo AF: 0.472

Asia WGS AF: 0.554 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		1.1
PromoterAI		-0.026	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1383914; hg19: chr8-26723049;