5-159870649-G-A

Position:

• chr5-159870649-G-A

Variant summary

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

The ENST00000641205.1(ADRA1B):​c.-256+5443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,244 control chromosomes in the GnomAD database, including 1,145 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 0.11 (1145 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADRA1B ENST00000641205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576

Genes affected

LINC01847 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1B	XM_011534435.2	c.-256+5443G>A		intron_variant			XP_011532737.1
ADRA1B	XM_047416776.1	c.-390+5443G>A		intron_variant			XP_047272732.1
LINC01847	NR_109891.1	n.736C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC01847	ENST00000522627.1	n.736C>T		non_coding_transcript_exon_variant	1/3	1
ADRA1B	ENST00000641205.1	c.-256+5443G>A		intron_variant				ENSP00000493019.1
LINC01847	ENST00000641163.1	n.182-2721C>T		intron_variant
ADRA1B	ENST00000641475.1	n.86+5443G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16202 AN: 152126 Hom.: 1145 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0716

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0714

Gnomad OTH AF: 0.0932

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.107 AC: 16226 AN: 152244 Hom.: 1145 Cov.: 33 AF XY: 0.106 AC XY: 7878 AN XY: 74440

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0778

Gnomad4 ASJ AF: 0.0813

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.0717

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.0714

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.0758 Hom.: 562

Bravo AF: 0.111

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6865665; hg19: chr5-159297656;