NM_053004.3:c.851C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_053004.3(GNB1L):c.851C>T(p.Thr284Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,612,600 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.015 ( 28 hom., cov: 33)

Exomes 𝑓: 0.019 ( 316 hom. )

Consequence

GNB1L
NM_053004.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.89

Variant links:

Genes affected

GNB1L (HGNC:4397): (G protein subunit beta 1 like) This gene encodes a G-protein beta-subunit-like polypeptide which is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 6 WD repeats and is highly expressed in the heart. The gene maps to the region on chromosome 22q11, which is deleted in DiGeorge syndrome, trisomic in derivative 22 syndrome and tetrasomic in cat-eye syndrome. Therefore, this gene may contribute to the etiology of those disorders. Transcripts from this gene share exons with some transcripts from the C22orf29 gene. [provided by RefSeq, Jul 2008]

GNB1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046129823).

BP6

Variant 22-19788842-G-A is Benign according to our data. Variant chr22-19788842-G-A is described in ClinVar as [Benign]. Clinvar id is 3042211.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0152 (2314/152362) while in subpopulation NFE AF= 0.0251 (1708/68024). AF 95% confidence interval is 0.0241. There are 28 homozygotes in gnomad4. There are 1056 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3 link	c.851C>T	p.Thr284Met	missense_variant	Exon 8 of 8	ENST00000329517.11	NP_443730.1	Q9BYB4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GNB1L	ENST00000329517.11 link	c.851C>T	p.Thr284Met	missense_variant	Exon 8 of 8	1	NM_053004.3	ENSP00000331313.6	Q9BYB4-1
GNB1L	ENST00000403325.5 link	c.851C>T	p.Thr284Met	missense_variant	Exon 7 of 7	1		ENSP00000385154.1	Q9BYB4-1
GNB1L	ENST00000405009.5 link	c.631-216C>T		intron_variant	Intron 7 of 7	1		ENSP00000384626.1	Q9BYB4-2
GNB1L	ENST00000460402.5 link	n.819C>T		non_coding_transcript_exon_variant	Exon 6 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2314

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00439

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00680

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0251

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0147

AC:

3629

AN:

246342

Hom.:

AF XY:

0.0148

AC XY:

1983

AN XY:

134358

show subpopulations

Gnomad AFR exome

AF:

0.00349

Gnomad AMR exome

AF:

0.00599

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.000442

Gnomad SAS exome

AF:

0.000818

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.0242

Gnomad OTH exome

AF:

0.0155

GnomAD4 exome

AF:

0.0194

AC:

28291

AN:

1460238

Hom.:

316

Cov.:

AF XY:

0.0189

AC XY:

13713

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.00649

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000916

Gnomad4 FIN exome

AF:

0.0265

Gnomad4 NFE exome

AF:

0.0229

Gnomad4 OTH exome

AF:

0.0159

GnomAD4 genome

AF:

0.0152

AC:

2314

AN:

152362

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.00438

Gnomad4 AMR

AF:

0.00679

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0250

Gnomad4 NFE

AF:

0.0251

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0207

Hom.:

Bravo

AF:

0.0132

TwinsUK

AF:

0.0251

AC:

ALSPAC

AF:

0.0234

AC:

ESP6500AA

AF:

0.00434

AC:

ESP6500EA

AF:

0.0242

AC:

207

ExAC

AF:

0.0148

AC:

1793

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0208

EpiControl

AF:

0.0184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GNB1L-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

0.080

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

.;D

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.18

Sift

Benign

0.033

D;D

Sift4G

Uncertain

0.031

D;D

Polyphen

0.97

D;D

Vest4

0.12

MPC

0.60

ClinPred

0.048

GERP RS

3.4

Varity_R

0.040

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

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