rs6052456

chr20-4244926-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.1111+2921G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,210 control chromosomes in the GnomAD database, including 2,567 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 0.18 (2567 hom., cov: 33)
• Consequence: ADRA1D NM_000678.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1D	NM_000678.4	c.1111+2921G>A		intron_variant		ENST00000379453.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1D	ENST00000379453.6	c.1111+2921G>A		intron_variant		1	NM_000678.4	P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26947 AN: 152092 Hom.: 2562 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.177 AC: 26977 AN: 152210 Hom.: 2567 Cov.: 33 AF XY: 0.173 AC XY: 12883 AN XY: 74422

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.175

Alfa AF: 0.204 Hom.: 5090

Bravo AF: 0.174

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.0
Dann	Benign	0.37

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: rs6052456; hg19: chr20-4225573;