rs946188

Variant names:

• chr20-4234669-A-G
• rs946188
• NM_000678.4:c.1112-12539T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000678.4(ADRA1D):​c.1112-12539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,216 control chromosomes in the GnomAD database, including 3,144 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 0.19 (3144 hom., cov: 32)
• Consequence: ADRA1D NM_000678.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1D	NM_000678.4	c.1112-12539T>C		intron_variant	Intron 1 of 1	ENST00000379453.6	NP_000669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1D	ENST00000379453.6	c.1112-12539T>C		intron_variant	Intron 1 of 1	1	NM_000678.4	ENSP00000368766.4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28429 AN: 152098 Hom.: 3142 Cov.: 32

Gnomad AFR AF: 0.0606

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.187 AC: 28433 AN: 152216 Hom.: 3144 Cov.: 32 AF XY: 0.184 AC XY: 13689 AN XY: 74416

African (AFR) AF: 0.0605 AC: 2514 AN: 41554

American (AMR) AF: 0.244 AC: 3738 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1011 AN: 3468

East Asian (EAS) AF: 0.237 AC: 1223 AN: 5160

South Asian (SAS) AF: 0.155 AC: 745 AN: 4812

European-Finnish (FIN) AF: 0.166 AC: 1764 AN: 10606

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16595 AN: 68006

Other (OTH) AF: 0.239 AC: 506 AN: 2114

Alfa AF: 0.222 Hom.: 7330

Bravo AF: 0.191

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		0.19
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: rs946188; hg19: chr20-4215316;