rs61767072

Positions:

• chr4-3767568-AGGGGGCGGGGCC-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM4 BP6 BA1

The NM_000683.4(ADRA2C):​c.971_982del​(p.Gly324_Ala327del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 1,097,418 control chromosomes in the GnomAD database, including 7,623 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (3700 hom., cov: 30)
  • Exomes 𝑓: 0.069 (3923 hom.)
• Consequence: ADRA2C NM_000683.4 inframe_deletion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.45

Genes affected

ADRA2C (HGNC:283): (adrenoceptor alpha 2C) Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. They include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. The mouse studies revealed that both the alpha2A and alpha2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons. The alpha2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha2C subtype modulated neurotransmission at lower levels of nerve activity. This gene encodes the alpha2C subtype, which contains no introns in either its coding or untranslated sequences. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000683.4.
• BP6: Variant 4-3767568-AGGGGGCGGGGCC-A is Benign according to our data. Variant chr4-3767568-AGGGGGCGGGGCC-A is described in ClinVar as [Benign]. Clinvar id is 18160.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA2C	NM_000683.4	c.971_982del	p.Gly324_Ala327del	inframe_deletion	1/1	ENST00000330055.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA2C	ENST00000330055.7	c.971_982del	p.Gly324_Ala327del	inframe_deletion	1/1		NM_000683.4	P1
ADRA2C	ENST00000509482.1	c.971_982del	p.Gly324_Ala327del	inframe_deletion	1/2	3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23104 AN: 146708 Hom.: 3683 Cov.: 30

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.0763

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.122 AC: 21 AN: 172 Hom.: 1 AF XY: 0.130 AC XY: 14 AN XY: 108

Gnomad SAS exome AF: 0.188

Gnomad NFE exome AF: 0.115

GnomAD4 exome AF: 0.0691 AC: 65644 AN: 950608 Hom.: 3923 AF XY: 0.0693 AC XY: 31127 AN XY: 449120

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.0979

Gnomad4 ASJ exome AF: 0.0907

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0154

Gnomad4 NFE exome AF: 0.0556

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.158 AC: 23153 AN: 146810 Hom.: 3700 Cov.: 30 AF XY: 0.155 AC XY: 11106 AN XY: 71550

Gnomad4 AFR AF: 0.408

Gnomad4 AMR AF: 0.0923

Gnomad4 ASJ AF: 0.0763

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0118

Gnomad4 NFE AF: 0.0494

Gnomad4 OTH AF: 0.132

Alfa AF: 0.113 Hom.: 279

Bravo AF: 0.168

Asia WGS AF: 0.117 AC: 372 AN: 3168

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

RECLASSIFIED - ADRB1 POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Apr 01, 2007

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61767072; hg19: chr4-3769295;