15-52122889-T-TAC

Position:

• chr15-52122889-T-TAC

Variant summary

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

The NM_016194.4(GNB5):​c.1177-123_1177-122dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 712,020 control chromosomes in the GnomAD database, including 357 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (325 hom., cov: 23)
  • Exomes 𝑓: 0.0088 (32 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-TAC is Benign according to our data. Variant chr15-52122889-T-TAC is described in ClinVar as [Benign]. Clinvar id is 1291625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNB5	NM_016194.4	c.1177-123_1177-122dupGT		intron_variant		ENST00000261837.12	NP_057278.2
GNB5	NM_006578.4	c.1051-123_1051-122dupGT		intron_variant			NP_006569.1
GNB5	NM_001379343.1	c.895-123_895-122dupGT		intron_variant			NP_001366272.1
GNB5	XM_011521162.4	c.1051-123_1051-122dupGT		intron_variant			XP_011519464.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5396 AN: 150888 Hom.: 324 Cov.: 23

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0131

Gnomad ASJ AF: 0.00924

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000970

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0214

GnomAD4 exome AF: 0.00877 AC: 4918 AN: 561032 Hom.: 32 AF XY: 0.00820 AC XY: 2497 AN XY: 304552

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.00859

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.00834

Gnomad4 SAS exome AF: 0.00809

Gnomad4 FIN exome AF: 0.00250

Gnomad4 NFE exome AF: 0.00332

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0358 AC: 5404 AN: 150988 Hom.: 325 Cov.: 23 AF XY: 0.0345 AC XY: 2546 AN XY: 73750

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0131

Gnomad4 ASJ AF: 0.00924

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.0000970

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.0211

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 18, 2019

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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;