Variant chr15-52180076-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016194.4(GNB5):c.127-197C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 531,916 control chromosomes in the GnomAD database, including 7,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2876 hom., cov: 33)

Exomes 𝑓: 0.16 ( 5070 hom. )

Consequence

GNB5
NM_016194.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.476

Variant links:

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]

GNB5 links:

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

CERNA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-52180076-G-C is Benign according to our data. Variant chr15-52180076-G-C is described in ClinVar as [Benign]. Clinvar id is 1277738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB5	NM_016194.4 linkuse as main transcript	c.127-197C>G		intron_variant		ENST00000261837.12
CERNA1	NR_102751.1 linkuse as main transcript	n.51G>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB5	ENST00000261837.12 linkuse as main transcript	c.127-197C>G	intron_variant		5	NM_016194.4	P3	O14775-1
CERNA1	ENST00000654724.1 linkuse as main transcript	n.49G>C	non_coding_transcript_exon_variant	1/3
CERNA1	ENST00000559779.2 linkuse as main transcript	n.78G>C	non_coding_transcript_exon_variant	1/3	3
GNB5	ENST00000560075.1 linkuse as main transcript	n.158-197C>G	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28176

AN:

152032

Hom.:

2866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.0844

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.180

GnomAD4 exome

AF:

0.162

AC:

61698

AN:

379766

Hom.:

5070

Cov.:

AF XY:

0.163

AC XY:

30691

AN XY:

188526

show subpopulations

Gnomad4 AFR exome

AF:

0.236

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.0669

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.185

AC:

28220

AN:

152150

Hom.:

2876

Cov.:

AF XY:

0.186

AC XY:

13859

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.0844

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.175

Hom.:

306

Bravo

AF:

0.199

Asia WGS

AF:

0.159

AC:

556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.6

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over