dbSNP rs749283750: NELFCD:p.Asp4Asn (chr20-58981319-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198976.4(NELFCD):c.10G>A(p.Asp4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 951,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

NELFCD
NM_198976.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Publications

0 publications found

Variant links:

Genes affected

NELFCD (HGNC:15934): (negative elongation factor complex member C/D) The NELF complex of proteins interacts with the DSIF protein complex to repress transcriptional elongation by RNA polymerase II. The protein encoded by this gene is an essential part of the NELF complex. Alternative translation initiation site usage results in the formation of two isoforms with different N-termini. [provided by RefSeq, Jul 2008]

NELFCD links:

ENSG00000285091 (HGNC:):

ENSG00000285091 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2628705).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198976.4. 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
	NELFCD	NM_198976.4	MANE Select	c.10G>A	p.Asp4Asn	missense	Exon 1 of 15	NP_945327.3	Q8IXH7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NELFCD	ENST00000652272.2	MANE Select	c.10G>A	p.Asp4Asn	missense	Exon 1 of 15	ENSP00000499018.1	Q8IXH7-4
NELFCD	ENST00000602795.6	TSL:1	c.64G>A	p.Asp22Asn	missense	Exon 1 of 15	ENSP00000473290.1	H0UI80
NELFCD	ENST00000460601.5	TSL:1	n.43G>A		non_coding_transcript_exon	Exon 1 of 16	ENSP00000436783.2	X6RLT1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000169

AC:

AN:

59344

AF XY:

0.0000295

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:

0.0000291

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000589

AC:

AN:

951062

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

450294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18690

American (AMR)

AF:

0.00

AC:

AN:

9562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7744

East Asian (EAS)

AF:

0.00

AC:

AN:

13252

South Asian (SAS)

AF:

0.00

AC:

AN:

21852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10228

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3558

European-Non Finnish (NFE)

AF:

0.0000660

AC:

AN:

833064

Other (OTH)

AF:

0.0000302

AC:

AN:

33112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000933

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

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.023

Eigen_PC

Benign

0.017

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.83

PhyloP100

1.3

PrimateAI

Pathogenic

0.93

Sift4G

Benign

0.11

Vest4

0.22

MVP

0.50

MPC

0.88

ClinPred

0.63

GERP RS

3.7

PromoterAI

-0.086

Neutral

(source)

gMVP

0.33

Mutation Taster

=80/20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over