Genetic Variant GNG4:c.*1956T>C (chr1-235550153-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_001098722.2(GNG4):c.*1956T>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 0.579 in 152,062 control chromosomes in the GnomAD database, including 26,132 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 0.58 ( 26128 hom., cov: 32)

Exomes 𝑓: 0.80 ( 4 hom. )

Consequence

GNG4
NM_001098722.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.515

Publications

5 publications found

Variant links:

Genes affected

GNG4 (HGNC:4407): (G protein subunit gamma 4) Predicted to enable G-protein beta-subunit binding activity. Involved in negative regulation of cell growth. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

GNG4 links:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GNG4	NM_001098722.2 link	c.*1956T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000391854.7	NP_001092192.1	P50150B1APZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GNG4	ENST00000391854.7 link	c.*1956T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001098722.2	ENSP00000375727.2		P50150
GNG4	ENST00000450593.5 link	c.*1956T>C		3_prime_UTR_variant	Exon 4 of 4	4		ENSP00000398629.1		P50150

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87998

AN:

151934

Hom.:

26115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.640

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.829

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.605

Gnomad OTH

AF:

0.608

GnomAD4 exome

AF:

0.800

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

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:

0.579

AC:

88044

AN:

152052

Hom.:

26128

Cov.:

AF XY:

0.580

AC XY:

43126

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.477

AC:

19772

AN:

41468

American (AMR)

AF:

0.640

AC:

9770

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

2158

AN:

3468

East Asian (EAS)

AF:

0.829

AC:

4279

AN:

5160

South Asian (SAS)

AF:

0.455

AC:

2193

AN:

4820

European-Finnish (FIN)

AF:

0.634

AC:

6706

AN:

10576

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.605

AC:

41147

AN:

67974

Other (OTH)

AF:

0.614

AC:

1293

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1886

3772

5659

7545

9431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.599

Hom.:

12806

Bravo

AF:

0.579

Asia WGS

AF:

0.628

AC:

2185

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.46

PhyloP100

-0.52

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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