NM_053004.3:c.851C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T284K) has been classified as Uncertain significance.

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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053004.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB1L	NM_053004.3	MANE Select	c.851C>T	p.Thr284Met	missense	Exon 8 of 8	NP_443730.1	Q9BYB4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNB1L	ENST00000329517.11	TSL:1 MANE Select	c.851C>T	p.Thr284Met	missense	Exon 8 of 8	ENSP00000331313.6	Q9BYB4-1
GNB1L	ENST00000403325.5	TSL:1	c.851C>T	p.Thr284Met	missense	Exon 7 of 7	ENSP00000385154.1	Q9BYB4-1
GNB1L	ENST00000405009.5	TSL:1	c.631-216C>T		intron	N/A	ENSP00000384626.1	Q9BYB4-2

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

GnomAD2 exomes

AF:

0.0147

AC:

3629

AN:

246342

AF XY:

0.0148

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 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

African (AFR)

AF:

0.00299

AC:

100

AN:

33476

American (AMR)

AF:

0.00649

AC:

290

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00199

AC:

AN:

26104

East Asian (EAS)

AF:

0.000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000916

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.0265

AC:

1379

AN:

52136

Middle Eastern (MID)

AF:

0.000874

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0229

AC:

25417

AN:

1111844

Other (OTH)

AF:

0.0159

AC:

959

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1604

3209

4813

6418

8022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

912

1824

2736

3648

4560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0152

AC:

2314

AN:

152362

Hom.:

Cov.:

AF XY:

0.0142

AC XY:

1056

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.00438

AC:

182

AN:

41594

American (AMR)

AF:

0.00679

AC:

104

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0250

AC:

266

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0251

AC:

1708

AN:

68024

Other (OTH)

AF:

0.0123

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

117

233

350

466

583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0210

Hom.:

101

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

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GNB1L-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

0.080

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PhyloP100

2.9

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.1

REVEL

Benign

0.18

Sift

Benign

0.033

Sift4G

Uncertain

0.031

Polyphen

0.97

Vest4

0.12

MPC

0.60

ClinPred

0.048

GERP RS

3.4

Varity_R

0.040

gMVP

0.43

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over