15-52122889-T-TACAC

Position:

• chr15-52122889-T-TACAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016194.4(GNB5):​c.1177-125_1177-122dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 715,104 control chromosomes in the GnomAD database, including 6,400 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (5111 hom., cov: 23)
  • Exomes 𝑓: 0.11 (1289 hom.)
• Consequence: GNB5 NM_016194.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.221

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 -10 ACMG points.

• BP6: Variant 15-52122889-T-TACAC is Benign according to our data. Variant chr15-52122889-T-TACAC is described in ClinVar as [Benign]. Clinvar id is 1296652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB5	NM_016194.4	c.1177-125_1177-122dupGTGT		intron_variant		ENST00000261837.12	NP_057278.2
GNB5	NM_006578.4	c.1051-125_1051-122dupGTGT		intron_variant			NP_006569.1
GNB5	NM_001379343.1	c.895-125_895-122dupGTGT		intron_variant			NP_001366272.1
GNB5	XM_011521162.4	c.1051-125_1051-122dupGTGT		intron_variant			XP_011519464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNB5	ENST00000261837.12	c.1177-122_1177-121insGTGT		intron_variant		5	NM_016194.4	ENSP00000261837.7

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31886 AN: 150862 Hom.: 5100 Cov.: 23

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.112 AC: 63461 AN: 564136 Hom.: 1289 AF XY: 0.113 AC XY: 34726 AN XY: 306266

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.0817

Gnomad4 ASJ exome AF: 0.0997

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.0963

Gnomad4 NFE exome AF: 0.0893

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.212 AC: 31934 AN: 150968 Hom.: 5111 Cov.: 23 AF XY: 0.209 AC XY: 15428 AN XY: 73726

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.189

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

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60072605; hg19: chr15-52415086;