Genetic Variant GNB2:c.268-11C>G (chr7-100677487-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005273.4(GNB2):c.268-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.027 in 1,613,168 control chromosomes in the GnomAD database, including 728 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 ( 52 hom., cov: 33)

Exomes 𝑓: 0.028 ( 676 hom. )

Consequence

GNB2
NM_005273.4 intron

Scores

Splicing: ADA: 0.0005857

Clinical Significance

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

Conservation

PhyloP100: 0.0790

Variant links:

Genes affected

GNB2 (HGNC:4398): (G protein subunit beta 2) 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. This gene contains a trinucleotide (CCG) repeat length polymorphism in its 5' UTR. [provided by RefSeq, Jul 2008]

GNB2 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=-0.8).

BP6

Variant 7-100677487-C-G is Benign according to our data. Variant chr7-100677487-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1195386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-100677487-C-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (3000/152362) while in subpopulation NFE AF= 0.0305 (2078/68032). AF 95% confidence interval is 0.0295. There are 52 homozygotes in gnomad4. There are 1415 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3000 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB2	NM_005273.4 link	c.268-11C>G		intron_variant	Intron 5 of 9	ENST00000303210.9	NP_005264.2	P62879-1Q6FHM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB2	ENST00000303210.9 link	c.268-11C>G		intron_variant	Intron 5 of 9	1	NM_005273.4	ENSP00000305260.4		P62879-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

3001

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00461

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00807

Gnomad FIN

AF:

0.0188

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0306

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0224

AC:

5585

AN:

249332

Hom.:

AF XY:

0.0228

AC XY:

3075

AN XY:

135090

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0492

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.0316

Gnomad OTH exome

AF:

0.0256

GnomAD4 exome

AF:

0.0277

AC:

40478

AN:

1460806

Hom.:

676

Cov.:

AF XY:

0.0275

AC XY:

19953

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00487

Gnomad4 AMR exome

AF:

0.0154

Gnomad4 ASJ exome

AF:

0.0527

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.0234

Gnomad4 NFE exome

AF:

0.0308

Gnomad4 OTH exome

AF:

0.0251

GnomAD4 genome

AF:

0.0197

AC:

3000

AN:

152362

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1415

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00459

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00787

Gnomad4 FIN

AF:

0.0188

Gnomad4 NFE

AF:

0.0305

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0272

Hom.:

Bravo

AF:

0.0194

Asia WGS

AF:

0.00577

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 05, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.0

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00059

dbscSNV1_RF

Benign

0.014

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