15-52124394-C-G

Position:

• chr15-52124394-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016194.4(GNB5):​c.1176+79G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 1,188,688 control chromosomes in the GnomAD database, including 4,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (2044 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2011 hom.)
• Consequence: GNB5 NM_016194.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.479

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-52124394-C-G is Benign according to our data. Variant chr15-52124394-C-G is described in ClinVar as [Benign]. Clinvar id is 1268830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNB5	NM_016194.4	c.1176+79G>C		intron_variant		ENST00000261837.12
GNB5	NM_001379343.1	c.894+79G>C		intron_variant
GNB5	NM_006578.4	c.1050+79G>C		intron_variant
GNB5	XM_011521162.4	c.1050+79G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNB5	ENST00000261837.12	c.1176+79G>C		intron_variant		5	NM_016194.4	P3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16887 AN: 152124 Hom.: 2037 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.0989

GnomAD4 exome AF: 0.0427 AC: 44229 AN: 1036446 Hom.: 2011 AF XY: 0.0413 AC XY: 21595 AN XY: 522832

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.0464

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.000507

Gnomad4 SAS exome AF: 0.0184

Gnomad4 FIN exome AF: 0.0226

Gnomad4 NFE exome AF: 0.0394

Gnomad4 OTH exome AF: 0.0504

GnomAD4 genome AF: 0.111 AC: 16928 AN: 152242 Hom.: 2044 Cov.: 32 AF XY: 0.106 AC XY: 7927 AN XY: 74450

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.0613

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0403

Gnomad4 OTH AF: 0.0979

Alfa AF: 0.0779 Hom.: 127

Bravo AF: 0.124

Asia WGS AF: 0.0320 AC: 110 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.82
CADD	Benign	2.8
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs6493536; hg19: chr15-52416591;