15-52184283-C-A

Variant names:

• chr15-52184283-C-A
• rs4494485
• NM_016194.4:c.126+268G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016194.4(GNB5):​c.126+268G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,214 control chromosomes in the GnomAD database, including 900 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.064 (900 hom., cov: 33)
• Consequence: GNB5 NM_016194.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.83

Genes affected

GNB5 (HGNC:4401): (G protein subunit beta 5) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. Alternatively spliced transcript variants encoding different isoforms exist. [provided by RefSeq, Jul 2008]

CERNA1 (HGNC:52664): (competing endogenous lncRNA 1 for miR-4707-5p and miR-4767)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-52184283-C-A is Benign according to our data. Variant chr15-52184283-C-A is described in ClinVar as [Benign]. Clinvar id is 1277164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB5	NM_016194.4	c.126+268G>T		intron_variant	Intron 2 of 12	ENST00000261837.12	NP_057278.2
CERNA1	NR_102751.1	n.529+3081C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB5	ENST00000261837.12	c.126+268G>T		intron_variant	Intron 2 of 12	5	NM_016194.4	ENSP00000261837.7

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9749 AN: 152096 Hom.: 899 Cov.: 33

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0788

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

GnomAD4 genome AF: 0.0642 AC: 9769 AN: 152214 Hom.: 900 Cov.: 33 AF XY: 0.0703 AC XY: 5231 AN XY: 74412

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.0302

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.0369

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0417 Hom.: 27

Bravo AF: 0.0717

Asia WGS AF: 0.307 AC: 1064 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.037
DANN	Benign	0.32

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: rs4494485; hg19: chr15-52476480;