chr20-4221394-T-A

Position:

• chr20-4221394-T-A

Variant summary

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

The NM_000678.4(ADRA1D):​c.*129A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,060,912 control chromosomes in the GnomAD database, including 80,942 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 0.32 (8647 hom., cov: 33)
  • Exomes 𝑓: 0.40 (72295 hom.)
• Consequence: ADRA1D NM_000678.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562

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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1D	NM_000678.4	c.*129A>T		3_prime_UTR_variant	2/2	ENST00000379453.6	NP_000669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1D	ENST00000379453	c.*129A>T		3_prime_UTR_variant	2/2	1	NM_000678.4	ENSP00000368766.4

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48694 AN: 151984 Hom.: 8643 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.395 AC: 359164 AN: 908812 Hom.: 72295 Cov.: 12 AF XY: 0.400 AC XY: 181763 AN XY: 454882

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.299

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.320 AC: 48717 AN: 152100 Hom.: 8647 Cov.: 33 AF XY: 0.321 AC XY: 23857 AN XY: 74376

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.345

Alfa AF: 0.338 Hom.: 1266

Bravo AF: 0.312

Asia WGS AF: 0.405 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.79

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: rs2236554; hg19: chr20-4202041; COSMIC: COSV65240664; COSMIC: COSV65240664;