Genetic Variant NM_053004.3:c.*1189C>T (chr22-19787520-G-A) – 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.*1189C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,510 control chromosomes in the GnomAD database, including 4,743 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 0.24 ( 4737 hom., cov: 33)

Exomes 𝑓: 0.18 ( 6 hom. )

Consequence

GNB1L
NM_053004.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.274

Publications

6 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNB1L	NM_053004.3 link	c.*1189C>T		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.*1189C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_053004.3	ENSP00000331313.6		Q9BYB4-1

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36975

AN:

152138

Hom.:

4723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.0982

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.181

AC:

AN:

254

Hom.:

Cov.:

AF XY:

0.180

AC XY:

AN XY:

194

show subpopulations

African (AFR)

AF:

0.100

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.175

AC:

AN:

206

Other (OTH)

AF:

0.188

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.243

AC:

37034

AN:

152256

Hom.:

4737

Cov.:

AF XY:

0.245

AC XY:

18248

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.291

AC:

12082

AN:

41540

American (AMR)

AF:

0.232

AC:

3553

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

745

AN:

3470

East Asian (EAS)

AF:

0.0982

AC:

508

AN:

5172

South Asian (SAS)

AF:

0.336

AC:

1621

AN:

4830

European-Finnish (FIN)

AF:

0.240

AC:

2548

AN:

10606

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.223

AC:

15150

AN:

68016

Other (OTH)

AF:

0.261

AC:

551

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1472

2945

4417

5890

7362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.230

Hom.:

7063

Bravo

AF:

0.244

Asia WGS

AF:

0.221

AC:

768

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

(source)

DANN

Benign

0.46

PhyloP100

0.27

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