20-4227580-C-G

Position:

• chr20-4227580-C-G

Variant summary

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

The NM_000678.4(ADRA1D):​c.1112-5450G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,464 control chromosomes in the GnomAD database, including 15,638 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 0.45 (15638 hom., cov: 29)
• Consequence: ADRA1D NM_000678.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1D	NM_000678.4	c.1112-5450G>C		intron_variant		ENST00000379453.6	NP_000669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1D	ENST00000379453.6	c.1112-5450G>C		intron_variant		1	NM_000678.4	ENSP00000368766	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68193 AN: 151346 Hom.: 15628 Cov.: 29

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.487

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.451 AC: 68243 AN: 151464 Hom.: 15638 Cov.: 29 AF XY: 0.452 AC XY: 33464 AN XY: 73976

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.492

Alfa AF: 0.427 Hom.: 1753

Bravo AF: 0.460

Asia WGS AF: 0.606 AC: 2106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.65
DANN	Benign	0.19

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: rs835879; hg19: chr20-4208227;