Genetic Variant NENF:p.Arg8Trp (chr1-212432965-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_013349.5(NENF):c.22C>T(p.Arg8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000068 in 999,652 control chromosomes in the GnomAD database, including 2 homozygotes. 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 (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 2 hom. )

Consequence

NENF
NM_013349.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.966

Publications

0 publications found

Variant links:

Genes affected

NENF (HGNC:30384): (neudesin neurotrophic factor) This gene encodes a neurotrophic factor that may play a role in neuron differentiation and development. A pseudogene of this gene is found on chromosome 12. Alternate splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2009]

NENF links:

ENSG00000287445 (HGNC:):

ENSG00000287445 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15055934).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013349.5. 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
	NENF	NM_013349.5	MANE Select	c.22C>T	p.Arg8Trp	missense	Exon 1 of 4	NP_037481.1	Q9UMX5
	NENF	NR_026598.2		n.46C>T		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NENF	ENST00000366988.5	TSL:1 MANE Select	c.22C>T	p.Arg8Trp	missense	Exon 1 of 4	ENSP00000355955.3	Q9UMX5
NENF	ENST00000949005.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 4	ENSP00000619064.1
NENF	ENST00000949004.1		c.22C>T	p.Arg8Trp	missense	Exon 1 of 3	ENSP00000619063.1

Frequencies

GnomAD3 genomes

AF:

0.000133

AC:

AN:

150032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00319

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.000485

GnomAD4 exome

AF:

0.0000565

AC:

AN:

849620

Hom.:

Cov.:

AF XY:

0.0000499

AC XY:

AN XY:

401188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16742

American (AMR)

AF:

0.000224

AC:

AN:

4458

Ashkenazi Jewish (ASJ)

AF:

0.00265

AC:

AN:

8308

East Asian (EAS)

AF:

0.000559

AC:

AN:

12512

South Asian (SAS)

AF:

0.00

AC:

AN:

16230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2086

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

745356

Other (OTH)

AF:

0.000128

AC:

AN:

31276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.593

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:

0.000133

AC:

AN:

150032

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

73188

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41212

American (AMR)

AF:

0.000199

AC:

AN:

15070

Ashkenazi Jewish (ASJ)

AF:

0.00319

AC:

AN:

3446

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67270

Other (OTH)

AF:

0.000485

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

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:

0.000142

Hom.:

Bravo

AF:

0.000121

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.028

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.97

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.59

REVEL

Benign

0.26

Sift

Uncertain

0.026

Sift4G

Uncertain

0.058

Polyphen

0.0

Vest4

0.20

MutPred

0.39

Loss of methylation at R8 (P = 0.0087)

MVP

0.45

MPC

0.047

ClinPred

0.12

GERP RS

-3.4

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.061

gMVP

0.52

Mutation Taster

=92/8

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