rs3730284

Positions:

• chr5-159917439-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_000679.4(ADRA1B):​c.534C>T​(p.Ile178=) 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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4007 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1B	NM_000679.4	c.534C>T	p.Ile178=	synonymous_variant	1/2	ENST00000306675.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1B	ENST00000306675.5	c.534C>T	p.Ile178=	synonymous_variant	1/2	1	NM_000679.4	P1
LINC01847	ENST00000641163.1	n.181+11596G>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.0257 AC: 6466 AN: 251426 Hom.: 137 AF XY: 0.0260 AC XY: 3528 AN XY: 135890

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 SAS exome AF: 0.00826

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

Gnomad4 AFR exome AF: 0.0116

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00898

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.0338

Gnomad4 OTH exome AF: 0.0270

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

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00685

Gnomad4 FIN AF: 0.0581

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0306 Hom.: 53

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.2
DANN	Benign	0.85

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: rs3730284; hg19: chr5-159344446;