chr5-159917439-C-T

Variant names:

• chr5-159917439-C-T
• rs3730284
• NM_000679.4:c.534C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_000679.4(ADRA1B):​c.534C>T​(p.Ile178Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,614,144 control chromosomes in the GnomAD database, including 881 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 0.026 (79 hom., cov: 32)
  • Exomes 𝑓: 0.030 (802 hom.)
• Consequence: ADRA1B NM_000679.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 5 publications found

Genes affected

ADRA1B (HGNC:278): (adrenoceptor alpha 1B) 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-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region. [provided by RefSeq, Jul 2008]

LINC01847 (HGNC:52662): (long intergenic non-protein coding RNA 1847)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.34 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0263 (4007/152254) while in subpopulation NFE AF = 0.0362 (2463/68022). AF 95% confidence interval is 0.035. There are 79 homozygotes in GnomAd4. There are 1937 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4007 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000679.4. 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
	ADRA1B	NM_000679.4	MANE Select	c.534C>T	p.Ile178Ile	synonymous	Exon 1 of 2	NP_000670.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	ENST00000306675.5	TSL:1 MANE Select	c.534C>T	p.Ile178Ile	synonymous	Exon 1 of 2	ENSP00000306662.3
	LINC01847	ENST00000641163.1		n.181+11596G>A		intron	N/A
	LINC01847	ENST00000816795.1		n.142+11596G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0263 AC: 4008 AN: 152136 Hom.: 79 Cov.: 32

Gnomad AFR AF: 0.0112

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0283

GnomAD2 exomes AF: 0.0257 AC: 6466 AN: 251426 AF XY: 0.0260

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.00931

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0588

Gnomad NFE exome AF: 0.0363

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0304 AC: 44450 AN: 1461890 Hom.: 802 Cov.: 31 AF XY: 0.0299 AC XY: 21720 AN XY: 727248

African (AFR) AF: 0.0116 AC: 387 AN: 33480

American (AMR) AF: 0.0109 AC: 489 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 428 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00898 AC: 775 AN: 86258

European-Finnish (FIN) AF: 0.0556 AC: 2972 AN: 53418

Middle Eastern (MID) AF: 0.0288 AC: 166 AN: 5768

European-Non Finnish (NFE) AF: 0.0338 AC: 37601 AN: 1112010

Other (OTH) AF: 0.0270 AC: 1630 AN: 60396

GnomAD4 genome AF: 0.0263 AC: 4007 AN: 152254 Hom.: 79 Cov.: 32 AF XY: 0.0260 AC XY: 1937 AN XY: 74444

African (AFR) AF: 0.0112 AC: 465 AN: 41550

American (AMR) AF: 0.0150 AC: 229 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00685 AC: 33 AN: 4816

European-Finnish (FIN) AF: 0.0581 AC: 616 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0362 AC: 2463 AN: 68022

Other (OTH) AF: 0.0280 AC: 59 AN: 2106

Alfa AF: 0.0315 Hom.: 156

Bravo AF: 0.0218

Asia WGS AF: 0.0130 AC: 47 AN: 3478

EpiCase AF: 0.0328

EpiControl AF: 0.0296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.2
DANN	Benign	0.85
PhyloP100		-0.34
Mutation Taster		=93/7	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: rs3730284; hg19: chr5-159344446;