5-159951575-G-C

Variant names:

• chr5-159951575-G-C
• rs6884129
• NM_000679.4:c.950-20304G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000679.4(ADRA1B):​c.950-20304G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 497,502 control chromosomes in the GnomAD database, including 3,150 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 0.12 (1132 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2018 hom.)
• Consequence: ADRA1B NM_000679.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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]

GAPDHP40 (HGNC:37797): (glyceraldehyde 3 phosphate dehydrogenase pseudogene 40)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1B	NM_000679.4	c.950-20304G>C		intron_variant	Intron 1 of 1	ENST00000306675.5	NP_000670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000306675.5	c.950-20304G>C		intron_variant	Intron 1 of 1	1	NM_000679.4	ENSP00000306662.3
GAPDHP40	ENST00000505218.1	n.-77C>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17531 AN: 151980 Hom.: 1128 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0974

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.102 AC: 35388 AN: 345404 Hom.: 2018 AF XY: 0.101 AC XY: 19083 AN XY: 188796

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.0659

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.0881

Gnomad4 FIN exome AF: 0.0984

Gnomad4 NFE exome AF: 0.0984

Gnomad4 OTH exome AF: 0.0995

GnomAD4 genome AF: 0.115 AC: 17563 AN: 152098 Hom.: 1132 Cov.: 32 AF XY: 0.114 AC XY: 8501 AN XY: 74374

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0951

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.0974

Gnomad4 OTH AF: 0.106

Alfa AF: 0.108 Hom.: 118

Bravo AF: 0.115

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.73

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: rs6884129; hg19: chr5-159378582;