rs3739216

Variant names:

• chr8-26769732-G-C
• rs3739216
• NM_000680.4:c.*417C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-26769732-G-C
• chr8-26769732-G-T

Variant summary

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

The NM_000680.4(ADRA1A):​c.*417C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 990,204 control chromosomes in the GnomAD database, including 4,363 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 0.12 (1786 hom., cov: 32)
  • Exomes 𝑓: 0.067 (2577 hom.)
• Consequence: ADRA1A NM_000680.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 10 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 = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.*417C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000380573.4	NP_000671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4	c.*417C>G		3_prime_UTR_variant	Exon 3 of 3	2	NM_000680.4	ENSP00000369947.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18870 AN: 152002 Hom.: 1787 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0670 AC: 56160 AN: 838084 Hom.: 2577 Cov.: 31 AF XY: 0.0666 AC XY: 25777 AN XY: 387162

African (AFR) AF: 0.203 AC: 3232 AN: 15924

American (AMR) AF: 0.146 AC: 204 AN: 1394

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 306 AN: 5340

East Asian (EAS) AF: 0.449 AC: 1683 AN: 3746

South Asian (SAS) AF: 0.176 AC: 2909 AN: 16546

European-Finnish (FIN) AF: 0.0407 AC: 17 AN: 418

Middle Eastern (MID) AF: 0.113 AC: 184 AN: 1630

European-Non Finnish (NFE) AF: 0.0587 AC: 44896 AN: 765490

Other (OTH) AF: 0.0989 AC: 2729 AN: 27596

GnomAD4 genome AF: 0.124 AC: 18886 AN: 152120 Hom.: 1786 Cov.: 32 AF XY: 0.126 AC XY: 9390 AN XY: 74400

African (AFR) AF: 0.193 AC: 8004 AN: 41470

American (AMR) AF: 0.156 AC: 2382 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0672 AC: 233 AN: 3466

East Asian (EAS) AF: 0.448 AC: 2316 AN: 5168

South Asian (SAS) AF: 0.192 AC: 922 AN: 4798

European-Finnish (FIN) AF: 0.0375 AC: 398 AN: 10610

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0635 AC: 4320 AN: 68004

Other (OTH) AF: 0.114 AC: 240 AN: 2114

Alfa AF: 0.0404 Hom.: 34

Bravo AF: 0.136

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.56
PhyloP100		-0.27
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: rs3739216; hg19: chr8-26627249;