Genetic Variant NELFE:p.Arg234Gln (chr6-31954596-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002904.6(NELFE):c.701G>A(p.Arg234Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000076 in 1,592,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

NELFE
NM_002904.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

Publications

1 publications found

Variant links:

Genes affected

NELFE (HGNC:13974): (negative elongation factor complex member E) The protein encoded by this gene is part of a complex termed negative elongation factor (NELF) which represses RNA polymerase II transcript elongation. This protein bears similarity to nuclear RNA-binding proteins; however, it has not been demonstrated that this protein binds RNA. The protein contains a tract of alternating basic and acidic residues, largely arginine (R) and aspartic acid (D). The gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. [provided by RefSeq, Jul 2008]

NELFE links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33268636).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002904.6. 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
	NELFE	NM_002904.6	MANE Select	c.701G>A	p.Arg234Gln	missense	Exon 7 of 11	NP_002895.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NELFE	ENST00000375429.8	TSL:1 MANE Select	c.701G>A	p.Arg234Gln	missense	Exon 7 of 11	ENSP00000364578.3	P18615-1
NELFE	ENST00000375425.9	TSL:2	c.722G>A	p.Arg241Gln	missense	Exon 7 of 11	ENSP00000364574.5	P18615-3
NELFE	ENST00000948308.1		c.719G>A	p.Arg240Gln	missense	Exon 8 of 12	ENSP00000618367.1

Frequencies

GnomAD3 genomes

AF:

0.0000800

AC:

AN:

150064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000950

AC:

AN:

221032

AF XY:

0.000136

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000558

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000756

AC:

109

AN:

1442262

Hom.:

Cov.:

AF XY:

0.0000881

AC XY:

AN XY:

715180

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33134

American (AMR)

AF:

0.0000230

AC:

AN:

43528

Ashkenazi Jewish (ASJ)

AF:

0.0000408

AC:

AN:

24502

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39564

South Asian (SAS)

AF:

0.0000366

AC:

AN:

81936

European-Finnish (FIN)

AF:

0.0000391

AC:

AN:

51204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5582

European-Non Finnish (NFE)

AF:

0.0000888

AC:

AN:

1103138

Other (OTH)

AF:

0.0000335

AC:

AN:

59674

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.0000799

AC:

AN:

150152

Hom.:

Cov.:

AF XY:

0.000137

AC XY:

AN XY:

73204

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41282

American (AMR)

AF:

0.00

AC:

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

5072

South Asian (SAS)

AF:

0.000212

AC:

AN:

4724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.000150

AC:

AN:

66742

Other (OTH)

AF:

0.00

AC:

AN:

2060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.000134

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.000133

AC:

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

0.23

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.073

MetaRNN

Benign

0.33

MetaSVM

Uncertain

-0.17

MutationAssessor

Pathogenic

3.0

PhyloP100

2.2

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.29

Sift

Uncertain

0.013

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.46

MVP

0.66

MPC

0.64

ClinPred

0.24

GERP RS

5.4

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.19

gMVP

0.23

Mutation Taster

=76/24

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

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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