rs6076639

Positions:

• chr20-4238611-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+9236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,166 control chromosomes in the GnomAD database, including 2,568 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 (2568 hom., cov: 31)
• Consequence: ADRA1D NM_000678.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1D	NM_000678.4	c.1111+9236G>A		intron_variant		ENST00000379453.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1D	ENST00000379453.6	c.1111+9236G>A		intron_variant		1	NM_000678.4	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27368 AN: 152048 Hom.: 2564 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.180 AC: 27402 AN: 152166 Hom.: 2568 Cov.: 31 AF XY: 0.176 AC XY: 13121 AN XY: 74392

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.0395

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.201

Alfa AF: 0.211 Hom.: 1931

Bravo AF: 0.176

Asia WGS AF: 0.113 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.57

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: rs6076639; hg19: chr20-4219258;