rs2195926

Positions:

• chr5-159895916-G-A
• chr5-159895916-G-C

Variant summary

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

The ENST00000641205.1(ADRA1B):​c.-255-20203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,102 control chromosomes in the GnomAD database, including 39,660 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 0.70 (39660 hom., cov: 32)
• Consequence: ADRA1B ENST00000641205.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1B	XM_011534435.2	c.-255-20203G>A		intron_variant			XP_011532737.1
ADRA1B	XM_047416776.1	c.-389-12730G>A		intron_variant			XP_047272732.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000641205.1	c.-255-20203G>A		intron_variant				ENSP00000493019.1
LINC01847	ENST00000641163.1	n.182-27988C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.704 AC: 107042 AN: 151986 Hom.: 39618 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.704 AC: 107122 AN: 152102 Hom.: 39660 Cov.: 32 AF XY: 0.694 AC XY: 51581 AN XY: 74358

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.697

Alfa AF: 0.630 Hom.: 2121

Bravo AF: 0.703

Asia WGS AF: 0.417 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2195926; hg19: chr5-159322923;