dbSNP rs3880457: NELFE:c.1046-44A>G (chr6-31952442-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002904.6(NELFE):c.1046-44A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,451,042 control chromosomes in the GnomAD database, including 97 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 0.0019 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 89 hom. )

Consequence

NELFE
NM_002904.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.22

Publications

5 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:

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=-0.93).

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELFE	NM_002904.6 link	c.1046-44A>G		intron_variant	Intron 10 of 10	ENST00000375429.8	NP_002895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELFE	ENST00000375429.8 link	c.1046-44A>G		intron_variant	Intron 10 of 10	1	NM_002904.6	ENSP00000364578.3

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

291

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0510

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00362

AC:

826

AN:

228360

AF XY:

0.00332

show subpopulations

Gnomad AFR exome

AF:

0.000385

Gnomad AMR exome

AF:

0.0000988

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0447

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000388

Gnomad OTH exome

AF:

0.000900

GnomAD4 exome

AF:

0.00217

AC:

2816

AN:

1298780

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1406

AN XY:

653696

show subpopulations

African (AFR)

AF:

0.000469

AC:

AN:

29834

American (AMR)

AF:

0.0000982

AC:

AN:

40720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23936

East Asian (EAS)

AF:

0.0665

AC:

2580

AN:

38826

South Asian (SAS)

AF:

0.000769

AC:

AN:

80638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52606

Middle Eastern (MID)

AF:

0.000400

AC:

AN:

5000

European-Non Finnish (NFE)

AF:

0.0000524

AC:

AN:

972444

Other (OTH)

AF:

0.00188

AC:

103

AN:

54776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

145

290

434

579

724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00194

AC:

296

AN:

152262

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000506

AC:

AN:

41534

American (AMR)

AF:

0.000196

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0511

AC:

265

AN:

5182

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00182

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.056

(source)

DANN

Benign

0.29

PhyloP100

-4.2

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

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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