chr8-26836456-G-T

Variant names:

• chr8-26836456-G-T
• rs488323
• NM_000680.4:c.883+27631C>A

Variant summary

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

The NM_000680.4(ADRA1A):​c.883+27631C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,954 control chromosomes in the GnomAD database, including 18,506 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 (18506 hom., cov: 32)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 5 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]

COX6B1P4 (HGNC:2284): (cytochrome c oxidase subunit 6B1 pseudogene 4)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	NM_000680.4	MANE Select	c.883+27631C>A		intron	N/A	NP_000671.2
	ADRA1A	NM_033303.4		c.883+27631C>A		intron	N/A	NP_150646.3
	ADRA1A	NM_033304.3		c.883+27631C>A		intron	N/A	NP_150647.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.883+27631C>A		intron	N/A	ENSP00000369947.3
	ADRA1A	ENST00000380586.5	TSL:1	c.883+27631C>A		intron	N/A	ENSP00000369960.1
	ADRA1A	ENST00000276393.8	TSL:1	c.883+27631C>A		intron	N/A	ENSP00000276393.4

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73146 AN: 151836 Hom.: 18503 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.458

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.482 AC: 73171 AN: 151954 Hom.: 18506 Cov.: 32 AF XY: 0.476 AC XY: 35327 AN XY: 74254

African (AFR) AF: 0.435 AC: 17991 AN: 41402

American (AMR) AF: 0.357 AC: 5450 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3468

East Asian (EAS) AF: 0.198 AC: 1018 AN: 5142

South Asian (SAS) AF: 0.282 AC: 1362 AN: 4822

European-Finnish (FIN) AF: 0.618 AC: 6526 AN: 10558

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37553 AN: 67974

Other (OTH) AF: 0.453 AC: 953 AN: 2104

Alfa AF: 0.469 Hom.: 6968

Bravo AF: 0.460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.57
PhyloP100		0.011
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: rs488323; hg19: chr8-26693973;