rs6052456

Variant names:

• chr20-4244926-C-T
• rs6052456
• NM_000678.4:c.1111+2921G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000298420 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000678.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1D	NM_000678.4	MANE Select	c.1111+2921G>A		intron	N/A	NP_000669.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1D	ENST00000379453.6	TSL:1 MANE Select	c.1111+2921G>A		intron	N/A	ENSP00000368766.4
	ENSG00000298420	ENST00000755410.1		n.50+2164C>T		intron	N/A

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

African (AFR) AF: 0.169 AC: 6996 AN: 41514

American (AMR) AF: 0.136 AC: 2085 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3472

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5176

South Asian (SAS) AF: 0.129 AC: 621 AN: 4822

European-Finnish (FIN) AF: 0.179 AC: 1899 AN: 10620

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14090 AN: 67994

Other (OTH) AF: 0.175 AC: 370 AN: 2114

Alfa AF: 0.198 Hom.: 8220

Bravo AF: 0.174

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.38
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: rs6052456; hg19: chr20-4225573;