Variant 15-52124357-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_016194.4(GNB5):c.1176+116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 763,066 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.020 ( 49 hom., cov: 32)

Exomes 𝑓: 0.024 ( 219 hom. )

Consequence

GNB5
NM_016194.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-52124357-C-T is Benign according to our data. Variant chr15-52124357-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1174285.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0202 (3074/152292) while in subpopulation NFE AF= 0.0314 (2136/68016). AF 95% confidence interval is 0.0303. There are 49 homozygotes in gnomad4. There are 1451 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GNB5	NM_016194.4 linkuse as main transcript	c.1176+116G>A	intron_variant	ENST00000261837.12
GNB5	NM_001379343.1 linkuse as main transcript	c.894+116G>A	intron_variant
GNB5	NM_006578.4 linkuse as main transcript	c.1050+116G>A	intron_variant
GNB5	XM_011521162.4 linkuse as main transcript	c.1050+116G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB5	ENST00000261837.12 linkuse as main transcript	c.1176+116G>A		intron_variant		5	NM_016194.4	P3	O14775-1

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3076

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0314

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.0242

AC:

14801

AN:

610774

Hom.:

219

AF XY:

0.0237

AC XY:

7525

AN XY:

317836

show subpopulations

Gnomad4 AFR exome

AF:

0.00481

Gnomad4 AMR exome

AF:

0.0184

Gnomad4 ASJ exome

AF:

0.0435

Gnomad4 EAS exome

AF:

0.000210

Gnomad4 SAS exome

AF:

0.00204

Gnomad4 FIN exome

AF:

0.0248

Gnomad4 NFE exome

AF:

0.0295

Gnomad4 OTH exome

AF:

0.0243

GnomAD4 genome

AF:

0.0202

AC:

3074

AN:

152292

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1451

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.0208

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0202

Gnomad4 NFE

AF:

0.0314

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.0205

Hom.:

Bravo

AF:

0.0190

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.050

DANN

Benign

0.45

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