Genetic Variant NM_001098722.2: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

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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