rs4815670

Variant names:

• chr20-4236217-A-G
• rs4815670
• NM_000678.4:c.1111+11630T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-4236217-A-G
• chr20-4236217-A-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.1111+11630T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,098 control chromosomes in the GnomAD database, including 21,848 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 0.53 (21848 hom., cov: 33)
• Consequence: ADRA1D NM_000678.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1D	NM_000678.4	c.1111+11630T>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.1111+11630T>C		intron_variant	Intron 1 of 1	1	NM_000678.4	ENSP00000368766.4

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80844 AN: 151978 Hom.: 21829 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.532 AC: 80910 AN: 152098 Hom.: 21848 Cov.: 33 AF XY: 0.533 AC XY: 39627 AN XY: 74356

African (AFR) AF: 0.489 AC: 20301 AN: 41476

American (AMR) AF: 0.522 AC: 7980 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1704 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1943 AN: 5172

South Asian (SAS) AF: 0.424 AC: 2044 AN: 4822

European-Finnish (FIN) AF: 0.651 AC: 6881 AN: 10566

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.565 AC: 38415 AN: 67996

Other (OTH) AF: 0.510 AC: 1078 AN: 2112

Alfa AF: 0.536 Hom.: 29357

Bravo AF: 0.521

Asia WGS AF: 0.395 AC: 1377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.8
DANN	Benign	0.82
PhyloP100		-0.91
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: rs4815670; hg19: chr20-4216864;