NM_000678.4:c.1111+9236G>A

Variant names:

• chr20-4238611-C-T
• rs6076639
• NM_000678.4:c.1111+9236G>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+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
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1D	NM_000678.4	MANE Select	c.1111+9236G>A		intron	N/A	NP_000669.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1D	ENST00000379453.6	TSL:1 MANE Select	c.1111+9236G>A		intron	N/A	ENSP00000368766.4

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

African (AFR) AF: 0.131 AC: 5437 AN: 41534

American (AMR) AF: 0.172 AC: 2624 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1062 AN: 3470

East Asian (EAS) AF: 0.0395 AC: 204 AN: 5168

South Asian (SAS) AF: 0.197 AC: 949 AN: 4816

European-Finnish (FIN) AF: 0.171 AC: 1813 AN: 10594

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14649 AN: 67976

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.201 Hom.: 6233

Bravo AF: 0.176

Asia WGS AF: 0.113 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.0
DANN	Benign	0.57
PhyloP100		0.87
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: rs6076639; hg19: chr20-4219258;