rs835882

Variant names:

• chr20-4229125-G-A
• rs835882
• NM_000678.4:c.1112-6995C>T

Variant summary

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

The NM_000678.4(ADRA1D):​c.1112-6995C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,226 control chromosomes in the GnomAD database, including 434 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 0.049 (434 hom., cov: 32)
• Consequence: ADRA1D NM_000678.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1D	NM_000678.4	c.1112-6995C>T		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.1112-6995C>T		intron_variant	Intron 1 of 1	1	NM_000678.4	ENSP00000368766.4

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7452 AN: 152108 Hom.: 433 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0296

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0568

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

GnomAD4 genome AF: 0.0490 AC: 7455 AN: 152226 Hom.: 434 Cov.: 32 AF XY: 0.0479 AC XY: 3563 AN XY: 74446

African (AFR) AF: 0.138 AC: 5736 AN: 41498

American (AMR) AF: 0.0298 AC: 456 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 123 AN: 3472

East Asian (EAS) AF: 0.0295 AC: 153 AN: 5182

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4822

European-Finnish (FIN) AF: 0.00452 AC: 48 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 757 AN: 68018

Other (OTH) AF: 0.0562 AC: 119 AN: 2116

Alfa AF: 0.0643 Hom.: 215

Bravo AF: 0.0559

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		0.62
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: rs835882; hg19: chr20-4209772;