rs3750625

Variant names:

• chr10-111079843-C-A
• rs3750625
• NM_000681.4:c.*449C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-111079843-C-A
• chr10-111079843-C-G
• chr10-111079843-C-T

Variant summary

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

The NM_000681.4(ADRA2A):​c.*449C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 182,962 control chromosomes in the GnomAD database, including 967 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 0.088 (883 hom., cov: 33)
  • Exomes 𝑓: 0.045 (84 hom.)
• Consequence: ADRA2A NM_000681.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 22 publications found

Genes affected

ADRA2A (HGNC:281): (adrenoceptor alpha 2A) Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. The alpha-2-adrenergic receptors are a type of adrenergic receptors (for adrenaline or epinephrine), which inhibit adenylate cyclase. These receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from sympathetic nerves and from adrenergic neurons in the central nervous system. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Studies in mouse revealed that both the alpha2A and alpha2C receptor subtypes were required for presynaptic transmitter release from the sympathetic nervous system in the heart and from central noradrenergic neurons. The alpha-2-adrenergic receptors are also involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. A clear association between the alpha-2-adrenergic receptor and disease has not been yet established. [provided by RefSeq, Sep 2019]

ADRA2A Gene-Disease associations (from GenCC):

• lipodystrophy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• lipodystrophy, familial partial, type 8

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000681.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA2A	NM_000681.4	MANE Select	c.*449C>A		3_prime_UTR	Exon 1 of 1	NP_000672.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA2A	ENST00000280155.4	TSL:6 MANE Select	c.*449C>A		3_prime_UTR	Exon 1 of 1	ENSP00000280155.2

Frequencies

GnomAD3 genomes AF: 0.0880 AC: 13389 AN: 152146 Hom.: 883 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0460

Gnomad OTH AF: 0.0784

GnomAD4 exome AF: 0.0451 AC: 1386 AN: 30698 Hom.: 84 Cov.: 0 AF XY: 0.0477 AC XY: 719 AN XY: 15086

African (AFR) AF: 0.172 AC: 93 AN: 540

American (AMR) AF: 0.0604 AC: 95 AN: 1574

Ashkenazi Jewish (ASJ) AF: 0.0578 AC: 23 AN: 398

East Asian (EAS) AF: 0.220 AC: 191 AN: 870

South Asian (SAS) AF: 0.219 AC: 202 AN: 922

European-Finnish (FIN) AF: 0.0140 AC: 211 AN: 15116

Middle Eastern (MID) AF: 0.111 AC: 6 AN: 54

European-Non Finnish (NFE) AF: 0.0488 AC: 500 AN: 10252

Other (OTH) AF: 0.0669 AC: 65 AN: 972

GnomAD4 genome AF: 0.0879 AC: 13384 AN: 152264 Hom.: 883 Cov.: 33 AF XY: 0.0873 AC XY: 6500 AN XY: 74446

African (AFR) AF: 0.168 AC: 6970 AN: 41544

American (AMR) AF: 0.0643 AC: 984 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3472

East Asian (EAS) AF: 0.190 AC: 983 AN: 5166

South Asian (SAS) AF: 0.161 AC: 774 AN: 4820

European-Finnish (FIN) AF: 0.0117 AC: 124 AN: 10620

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0460 AC: 3129 AN: 68018

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0500 Hom.: 126

Bravo AF: 0.0937

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.6
DANN	Benign	0.66
PhyloP100		0.64
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: rs3750625; hg19: chr10-112839601;