Variant chr15-52180219-G-T 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.127-340C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 170,534 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 144 hom., cov: 33)

Exomes 𝑓: 0.022 ( 12 hom. )

Consequence

GNB5
NM_016194.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0580

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-52180219-G-T is Benign according to our data. Variant chr15-52180219-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 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.127-340C>A		intron_variant		ENST00000261837.12
CERNA1	NR_102751.1 linkuse as main transcript	n.194G>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB5	ENST00000261837.12 linkuse as main transcript	c.127-340C>A		intron_variant		5	NM_016194.4	P3	O14775-1
CERNA1	ENST00000654724.1 linkuse as main transcript	n.192G>T		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.0266

AC:

4044

AN:

152210

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.00442

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0117

Gnomad OTH

AF:

0.0263

GnomAD4 exome

AF:

0.0224

AC:

407

AN:

18206

Hom.:

Cov.:

AF XY:

0.0229

AC XY:

208

AN XY:

9090

show subpopulations

Gnomad4 AFR exome

AF:

0.0443

Gnomad4 AMR exome

AF:

0.00758

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.00739

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.0265

AC:

4043

AN:

152328

Hom.:

144

Cov.:

AF XY:

0.0278

AC XY:

2072

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0398

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.00442

Gnomad4 NFE

AF:

0.0117

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.119

AC:

414

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.9

DANN

Benign

0.84

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

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