Genetic Variant GNB1L:c.*945T>C (chr22-19787764-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_053004.3(GNB1L):c.*945T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,226 control chromosomes in the GnomAD database, including 14,375 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14370 hom., cov: 34)

Exomes 𝑓: 0.30 ( 5 hom. )

Consequence

GNB1L
NM_053004.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0800

Publications

18 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3 link	c.*945T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000329517.11	NP_443730.1	Q9BYB4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNB1L	ENST00000329517.11 link	c.*945T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_053004.3	ENSP00000331313.6		Q9BYB4-1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64241

AN:

152008

Hom.:

14334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.576

Gnomad SAS

AF:

0.562

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.428

GnomAD4 exome

AF:

0.300

AC:

AN:

100

Hom.:

Cov.:

AF XY:

0.292

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.278

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.423

AC:

64331

AN:

152126

Hom.:

14370

Cov.:

AF XY:

0.427

AC XY:

31786

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.535

AC:

22180

AN:

41490

American (AMR)

AF:

0.475

AC:

7270

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1540

AN:

3466

East Asian (EAS)

AF:

0.575

AC:

2970

AN:

5166

South Asian (SAS)

AF:

0.561

AC:

2703

AN:

4822

European-Finnish (FIN)

AF:

0.300

AC:

3173

AN:

10584

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.339

AC:

23069

AN:

67990

Other (OTH)

AF:

0.426

AC:

900

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1935

3870

5804

7739

9674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.385

Hom.:

33140

Bravo

AF:

0.440

Asia WGS

AF:

0.532

AC:

1847

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

(source)

DANN

Benign

0.20

PhyloP100

-0.080

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over