20-4234910-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000678.4(ADRA1D):c.1112-12780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,918 control chromosomes in the GnomAD database, including 15,247 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 0.43 (15247 hom., cov: 32)
• Consequence: ADRA1D NM_000678.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186

Genes affected

ADRA1D (HGNC:280): (adrenoceptor alpha 1D) 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-1D-adrenergic receptor. Similar to alpha-1B-adrenergic receptor gene, this gene comprises 2 exons and a single intron that interrupts the coding region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1D	NM_000678.4	c.1112-12780G>A		intron_variant		ENST00000379453.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1D	ENST00000379453.6	c.1112-12780G>A		intron_variant		1	NM_000678.4	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65037 AN: 151800 Hom.: 15234 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.428 AC: 65085 AN: 151918 Hom.: 15247 Cov.: 32 AF XY: 0.431 AC XY: 31970 AN XY: 74238

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.405

Alfa AF: 0.501 Hom.: 10466

Bravo AF: 0.402

Asia WGS AF: 0.361 AC: 1258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.2
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556832; hg19: chr20-4215557;