8-26866301-C-T

Variant names:

• chr8-26866301-C-T
• rs573542
• NM_000680.4:c.-687+635G>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.-687+635G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,200 control chromosomes in the GnomAD database, including 62,522 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 0.90 (62522 hom., cov: 32)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 7 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]

ENSG00000303788 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.-687+635G>A		intron_variant	Intron 1 of 2	ENST00000380573.4	NP_000671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4	c.-687+635G>A		intron_variant	Intron 1 of 2	2	NM_000680.4	ENSP00000369947.3
ENSG00000303788	ENST00000797227.1	n.124+10C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137490 AN: 152082 Hom.: 62486 Cov.: 32

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.908

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

GnomAD4 genome AF: 0.904 AC: 137579 AN: 152200 Hom.: 62522 Cov.: 32 AF XY: 0.905 AC XY: 67336 AN XY: 74426

African (AFR) AF: 0.803 AC: 33323 AN: 41520

American (AMR) AF: 0.888 AC: 13597 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3433 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4681 AN: 5148

South Asian (SAS) AF: 0.933 AC: 4501 AN: 4822

European-Finnish (FIN) AF: 0.942 AC: 9999 AN: 10610

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64961 AN: 68004

Other (OTH) AF: 0.903 AC: 1910 AN: 2114

Alfa AF: 0.923 Hom.: 9480

Bravo AF: 0.896

Asia WGS AF: 0.897 AC: 3120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.83
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs573542; hg19: chr8-26723818;