rs1440828796

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005262.3(GFER):c.34G>A(p.Gly12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,475,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G12A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GFER
NM_005262.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -1.88

Publications

2 publications found

Variant links:

Genes affected

GFER (HGNC:4236): (growth factor, augmenter of liver regeneration) The hepatotrophic factor designated augmenter of liver regeneration (ALR) is thought to be one of the factors responsible for the extraordinary regenerative capacity of mammalian liver. It has also been called hepatic regenerative stimulation substance (HSS). The gene resides on chromosome 16 in the interval containing the locus for polycystic kidney disease (PKD1). The putative gene product is 42% similar to the scERV1 protein of yeast. The yeast scERV1 gene had been found to be essential for oxidative phosphorylation, the maintenance of mitochondrial genomes, and the cell division cycle. The human gene is both the structural and functional homolog of the yeast scERV1 gene. [provided by RefSeq, Jul 2008]

GFER links:

NOXO1 (HGNC:19404): (NADPH oxidase organizer 1) This gene encodes an NADPH oxidase (NOX) organizer, which positively regulates NOX1 and NOX3. The protein contains a PX domain and two SH3 domains. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

NOXO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062068224).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005262.3. 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
	GFER	NM_005262.3	MANE Select	c.34G>A	p.Gly12Ser	missense	Exon 1 of 3	NP_005253.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GFER	ENST00000248114.7	TSL:1 MANE Select	c.34G>A	p.Gly12Ser	missense	Exon 1 of 3	ENSP00000248114.6	P55789-1
NOXO1	ENST00000862126.1		c.-417C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000532185.1
NOXO1	ENST00000862127.1		c.-623C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000532186.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

80636

AF XY:

0.0000216

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000113

AC:

AN:

1323714

Hom.:

Cov.:

AF XY:

0.00000919

AC XY:

AN XY:

652686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26492

American (AMR)

AF:

0.00

AC:

AN:

26422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23188

East Asian (EAS)

AF:

0.00

AC:

AN:

29826

South Asian (SAS)

AF:

0.00

AC:

AN:

72716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4786

European-Non Finnish (NFE)

AF:

0.0000124

AC:

AN:

1052522

Other (OTH)

AF:

0.0000364

AC:

AN:

54894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.0000329

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.4

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.076

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-1.9

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.36

REVEL

Benign

0.012

Sift

Benign

0.55

Sift4G

Benign

0.44

Polyphen

0.043

Vest4

0.11

MutPred

0.24

Gain of phosphorylation at G12 (P = 0.0506)

MVP

0.52

MPC

0.32

ClinPred

0.030

GERP RS

-1.2

PromoterAI

0.063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.030

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over